RARE DISEASES

Projekte

Programme Review 2014

Research Going Beyond

GRSTIFTUNG.CH

1

RARE DISEASES – APPROACHES Rare Diseases – NEW New Approaches 2011

Contents:

First and foremost, the science has to be right …

Robert Slooves, Geneva Biotech Center

For these patients, there is no hope at the moment …

Botond Roska, Friedrich Miescher Institute

PAGE 2: BIOTECH COMPANIES FOCUSING ON ORPHAN DRUGS: A RARE PHENOMENON IN SWITZERLAND

PAGE 4: GENE THERAPY TACKLES RARE EYE DISEASE

PAGE 7: THE 2ND INTERNATIONAL CONGRESS ON RESEARCH OF RARE AND ORPHAN DISEASES

Many people ask me why I work on a disease that affects so few patients …

She knows that her life will never be the same …

When it comes to hope for a cure, then research tops the list …

PAGE 10: I FEEL A GREAT RESPONSIBILITY TO THE PATIENTS.

PAGE 12: MOST OF ALL, I MISS THE INDEPENDENCE.

Priya, a Wilson’s disease patient

Gisou van der Goot, EPFL

2

Esther Neiditsch, ProRaris

PAGE 15: WE ARE COMMITTED TO THE PATIENTS.

EDITORIAL

Our research priorities are not determined by potential market size …

Pascal Brenneisen, Novartis Switzerland

PAGE 8: A LOOK AT SOME OF THE CHALLENGES

Research Going Beyond

HEADING IN THE RIGHT DIRECTION

With the goal of developing diagnostics and drugs for treating rare diseases, in 2009 Gebert Rüf Stiftung began funding research in this often-neglected area. Since then, five annual calls for project submission have been made.

Swiss research groups have prepared and submitted some 338 proposals to our foundation; of these, 26 have been accepted with a budget totalling CHF 10.3 million. Almost half of these endeavours have achieved a diagnostic or therapeutic success.

In order to promote the development and the transfer to market of these promising projects, a collaboration has been launched with the newlyformed biotech company, Geneva Biotech Center. With the help of investors, potential drugs and therapies reach market maturity earlier than they would otherwise. These past years have not been dormant: Significant successes have been achieved at many levels, and progress continues to evolve. Indeed, the development of a long-overdue national strategy has been launched by the government. The umbrella organisation, ProRaris, was founded in 2010. In March 2014, the 2nd International Congress on Rare Diseases RE(ACT) will take place in Basel, bringing together the world’s leading scientists and other stakeholders. And, last but not least, one sees a clear trend of establishing centres of excellence in Switzerland.

For example, the Rare Disease Initiative Zurich (RaDIZ), whose aims are to improve care and treatment of patients with rare diseases and, simultaneously, position Zurich as a leading European research hub for rare diseases.

Nevertheless, gaps still exist. To address these short-comings, the RE(ACT) community was formed. This project seeks to improve the networking opportunities between the research community in academia and industry with the afflicted patients and their organisations (more on page 7). Here, as with so many other ventures, we are heading in the right direction but have not yet reached the goal.

PAGE 16: ALL RESEARCH PROJECTS AT A GLANCE

Pascale Vonmont Gebert Rüf Stiftung

3

RARE DISEASES – NEW APPROACHES

Biotech companies focusing on orphan drugs: a rare phenomenon in Switzerland

J

ust like the diseases on which they focus, biotech companies working on the development of drugs for rare diseases are themselves rare in Switzerland. According to Domenico Alexakis, CEO of the Swiss Biotech Association, the number of rare disease-focussed biotech firms that also conduct research in Switzerland can be counted on one hand.

This is quite disappointing as some excellent basic research is being carried out in this field in Switzerland.

Why then this unsatisfactory situation? According to Alexakis, the biggest challenge to starting a biotech project is the difficulty in finding funding.

In the biotech industry, this is a fundamental challenge because the prospects of resounding success are low and the development cycles long. For rare diseases, there are often additional hurdles, such as small sales markets. These factors make financing even tougher.

But in addition to traditional investors, so-called “business angels” are also active in the field of rare diseases. In contrast to a classical investor, a business angel plans differently and is more willing to invest for emotional or empathic reasons; indeed, maybe even coming on board just

4

BIOTECH COMPANIES FOCUSING ON ORPHAN DRUGS: A RARE PHENOMENON IN SWITZERLAND

Learning from other countries A study of EuropaBio, a European platform for the biotech industry, shows that, in certain countries (France, for example), where there is a national action plan on rare diseases in place, more research and development is carried out. The analysis further shows the advantages of the EU Directive that aims to facilitate the development of orphan drugs. The EU grants orphan drugs extended patent protection, as well as 10-year market exclusivity. The introduction of this directive has brought some progress: In the EU, the number of employees engaged in research into orphan drugs has more than doubled, from 2,000 to 5,000 since the year 2000. In addition, investments have increased by more than 200 percent. According to the study, the EU Directive is primarily responsible for these encouraging developments.

In comparison with other European countries, Switzerland has adopted more of a wait-and-see attitude. To date, it has implemented no comparable concessions, though in recent years, some projects along these lines have been initiated (see page 8).

Analysis of the EU Directive > www.ohe.org/publications/article/assessment-of-the-impact-of-orphan-medicinal-products-on-europe-15.cfm French National Action Plan > www.orpha.net/actor/Orphanews/2011/doc/Plan_national_maladies_rares.pdf

because there is no therapy for the diseased patients or because many children are afflicted. “Perhaps you should also increasingly think of business angels in the early stages of financing,” says Alexakis.

One company dares to try One company that is trying to forge its way despite the many obstacles, is the newly-established Geneva Biotech Center (GBC). This organisation, consisting of a team of experts from the former Geneva headquarters of Merck Serono, and headed by Robert Slooves, has set as its goal the bridging of the gap between academic research and pharmaceutical development. It is jumping into the void created by the – in some cases sharp – drop in pharmaceutical research seen in recent years.

Slooves is aware that it will be no easy task. And he speaks from experience: At Merck Serono, he worked on Kuvan, a drug for phenylketonuria, another rare disease. He also gained experience with Rebif, a drug for multiple sclerosis. “Rebif was actually an orphan drug in the beginning because, at the time, MS was little known and, accordingly, underdiagnosed.”

Slooves knows how to make money with orphan drugs. “First and foremost, the science has to be right, otherwise it won’t work.” Without a good foundation, there will always be problems, right up to the approval by insurance companies that are reluctant to pay for substances when efficacy has not been well-documented. Basically, the research

and development costs are only really covered if the active ingredient can additionally be used for the treatment of other diseases – or the development costs are low enough (as is the case with some orphan drugs).

Due to the myriad of challenges associated with the start-up of a biotech company that focuses on orphan drugs, framework conditions are critical for Slooves. It takes concessions to encourage the development of orphan drugs. In this respect, Switzerland still has some catching up to do compared with the EU (see box).

“Those cantons that seek to promote innovation could offer concessions in the field of rare diseases,” says Slooves.

>

www.genevabiotechcenter.com

5

RARE DISEASES – NEW APPROACHES

6

GENE THERAPY TACKLES RARE EYE DISEASE

Gene therapy tackles rare eye disease

P

atients who suffer from the rare genetic disorder, retinitis pigmentosa, are powerless to avert the outcome: sooner or later, little by little, they go blind. Their peripheral vision slowly constricts and tunnel vision ensues – a tunnel in the dark. Initially, it becomes difficult to see at dusk and at night, but later, also during the day.

In Switzerland, though precise figures are unavailable, an estimated 3,000 – 4,000 people are affected by this disease. “For these patients, there is no hope at the moment,” says Botond Roska, researcher at the Friedrich Miescher Institute and head of the project funded by Gebert Rüf Stiftung, Optogenic Vision Restoration and Neuroprotection in Retinitis Pigmentosa. “Over years or even decades, they live with the helplessness of seeing their eyesight fail.”

For nearly 20 years, the Hungarian-born scientist has explored the properties of the retina, the light-sensitive membrane where nerve cells convert light signals into electrical impulses. For several years, Roska and his team have been investigating a new and promising genetic approach, called optogenetics, to help retinitis pigmentosa patients. The patient is injected with a gene that directs the production of a protein that stimulates diseased retinal nerve cells to again relay information. The researchers have already demonstrated that this intervention works in mice. Their collaborators, led by José Sahel, are now testing the approach in primates.

“Of course, we know that projects like this entail considerable risks, especially when you move from animals to humans, but based on the

7

RARE DISEASES – NEW APPROACHES

previous data, we are hopeful about the next steps,” says Roska. The plan is for the first patients to be treated in 2015. The researchers can draw on the experience gathered in 180 patients who have already been injected with gene therapy vectors using different gene therapy methods.

If all goes according to plan, after having undergone successful gene therapy treatment and with the help of special glasses, patients may see again in black and white and even be able to perceive structures.

The tunnel may reopen, letting in some light.

More information on the project on page 17.

In Paris in 2011, Roska and others, including José Sahel, founded the company, GenSight, so that the next step, conducting clinical trials, could be initiated. “With Bernard Gilly as CEO, we have a strong team,” says Roska delightedly.

A milestone In June 2013 GenSight celebrated a milestone: Several investors – including Novartis Venture Fund – committed an investment sum of 32 million Euros to carry out the first clinical trials. What is particularly interesting for investors is that GenSight’s gene therapy approach could be used to treat similar diseases of the retina. This raises the possibility that other groups of patients could benefit from this therapy.

The fact that the new company is based in Paris is no coincidence.

In France, many medical procedures, including the treatment of rare diseases, are centralised at a few specific centres. Many patients suffering from retinitis pigmentosa are treated at a Parisian eye hospital led

by José Sahel. “This is an advantage for us, because it makes the search for patients considerably easier,” says Roska.

8

> www.gensight-biologics.com > www.fmi.ch/research/groupleader/?group=112

RE(ACT) CONGRESS

RE(ACT) 2014 2ND INTERNATIONAL CONGRESS ON RESEARCH OF RARE AND ORPHAN DISEASES The RE(ACT) Congress in March 2014 brings together researchers from around the world to discuss the latest results in the field of Rare and Orphan Diseases.

From March 5 to 8, 2014, the second RE(ACT) Congress will be held in Basel. What is especially noteworthy about this congress is the breadth of topics. Leading international researchers in the fields of stem cells, cell biology, gene therapy and genetic engineering will discuss and present their latest research projects and results in the field of rare diseases.

The congress is also of interest for industry representatives and representatives of patients and patient organisations. The organisers of the conference have the following goals:

RE(ACT) Community Scientists and patients in one network Patients often have a great deal of knowledge about their own disease, and sometimes information that even doctors and / or scientist do not possess. It is well-established that patients and patient organisations would like to start and finance research projects themselves. However, they often do not know exactly which researchers have the necessary tools and scientific knowledge to truly help them. Wellintended research projects sometimes veer off in the wrong direction or end up with useless results. This is expensive and frustrating for all involved. The online RE(ACT) Community, initiated by BLACKSWAN Foundation and Gebert Rüf Stiftung, aims to strengthen and coalesce the synergies between researchers and other stakeholders of rare and orphan diseases. On a specific section of the platform, the community will offer visibility concerning issues of crowd funding and of research projects declared eligible for funding by the RE(ACT) Scientific Advisory Board.

The RE(ACT) Community website (www.react-community.org) will have a dedicated members’ area, members’list, a database of laboratories and research scientist profiles, the logos of associations and sponsors, as well as a forum organised around four main topics dedicated to research, exchange of information and funding: Learn, Meet, Share and Fund.

Learn: from the knowledge and experience of other researchers and patients; Meet: other researchers and patients; Share: your scientific knowledge and experience; Fund: new research projects.

• Promote research on rare and orphan diseases among the general public, industry and policy makers; • Bring together researchers and their knowledge; • Facilitate the understanding of other more common diseases; • Encourage clear insights and positions from the scientific community at universities and industry.

One highlight will be the opening ceremony that will take place at 6 p.m. on March 5 2014 at the Conference Centre of the Gehry Building, one of the main buildings of Novartis Campus. Participants include Prof. Stephen Groft, Director of the Office of Rare Diseases Research at the National Institutes of Health in the United States.

Yann Le Cam, Director of the European patient organisation, Eurordis, will also speak at this public event. Pascal Brenneisen, Country President Novartis Switzerland says, “We feel honoured that we have been asked for the second time to host the RE(ACT) Congress on our Campus, and are happy to welcome again the leading rare disease researchers from around the globe in Basel.”

The congress was initiated by BLACKSWAN Foundation and Gebert Rüf Stiftung (Rare Diseases – New Approaches programme), and is supported by Eurordis (Rare Diseases Europe), ProRaris (Swiss Rare Disease Alliance) and E-Rare (ERA-Net).

Registration is possible until 18 January 2014. On-site registrations will be accepted subject to availability. > www.react-congress.org

9

RARE DISEASES – NEW APPROACHES

A look at some of the challenges “ In the field of rare diseases, government action attempts to find solutions to facilitate a rapid and accurate diagnosis and treatment, as well as secure funding for therapies.

Good coordination between specialists, research support, optimal transmission of knowledge and authorities that work together at federal, cantonal and international levels are essential.”

Caroline Clarinval, Project head Rare Diseases, Federal Office of Public Health

“ Our research priorities are not determined by potential market size. We choose to work where there is unmet medical need and where the scientific understanding is strongest.”

Pascal Brenneisen, Country President Novartis Switzerland

10

he first steps, at least, have been taken in Switzerland: The Swiss Federal Office of Public Health (BAG) has started to develop a national strategy. The Swiss National Science Foundation has chosen to participate in the European research programme, E-Rare, and accord higher priority to the topic of rare diseases. In recent years, patient organisations and reference centres have been set up.

But there is still a long way to go. Improvements are needed at many levels: For example, though there were appeals from various parties, the new drug law offers hardly any incentive to facilitate orphan drug development. This despite the well-documented fact that similar incentives in the US and the EU have led to more research and more orphan drugs being developed. Some 80 % of all clinical trials for orphan drugs are carried out in countries that have a national strategy in this area.

Swissmedic granted simplified approval and the BAG has adopted a regulation to facilitate the funding of orphan drugs. However, one part of this regulation has caused havoc: Health insurance companies can now decide independently whether or not they will pay for a drug.

And on the matter of approvals, though Switzerland might boast that today more than 100 orphan drugs have been authorised (though most of these are not automatically covered by health insurance), but in the US, this number tops 400.

A LOOK AT SOME OF THE CHALLENGES

Does the orphan drug model have a future?

The cited considerations raise the question, “Will the orphan drug model, which is based on various incentives for pharmaceutical manufacturers, be a victim of its own success in the future?” This problem is clearly illustrated in the field of oncology where individual cancers are categorised into increasingly narrower sub-groups.

Ultimately, each group becomes a rare disease in itself. One strong impetus behind this development is so-called “personalised medicine”.

Technically, the division into ever-smaller patient groups makes sense – side effects are reduced and the efficacy of an active ingredient can be increased. But are these subgroups truly rare diseases that should benefit from orphan drug status? Critics are sceptical here and see the danger that “arbitrary” subgroups could be identified that would then benefit from orphan drug status. This contradicts the original idea of supporting rare diseases

“ What is needed for rare disease patients in Switzerland to get better treatment? Interdisciplinary research centres and international research networks for rare diseases in order to optimise clinical and genetic diagnosis, research, teaching and therapy would be beneficial. Also, centralised registration of patients to enable follow-up and therapy studies, as well as special programmes to support targeted research projects that identify the genetic causes and pathomechanisms, as well as international clinical trials.”

Aysim Yilmaz, Head of Division Biology & Medicine, Swiss National Science Foundation

“ Often, the biggest problem for patients with a rare disease is the lack of hope for a cure. Frequently, the patients and their families despair because their treatment is not partially or completely reimbursed by their insurers.”

Esther Neiditsch, Managing Director of ProRaris, the Alliance of Rare Diseases Switzerland > www.bag.admin.ch/themen/medizin/13248/index.html

11

RARE DISEASES – NEW APPROACHES

“I feel a great responsibility to the patients.“

yaline fibromatosis (HF) is an extremely rare disease; worldwide only about 200 cases have been documented. People who suffer from this genetic disorder often live in isolation because, due to a genetic mutation, they are disfigured. Bumps as big as grapefruits can grow on the fingers, on the head and on the buttocks. Because the disease is so rare, most doctors are clueless when faced with an HF patient. And if patients are lucky enough to find a doctor who can diagnose the disease correctly, they have the misfortune to hear in the next breath that, regrettably, there is no treatment or cure. Only the bumps can be partially removed surgically. Many patients end up wheelchair-bound because the joints are affected. The most severe form of HF disease results in death before a child is two years old.

For several years, patients have looked with hope to the laboratory of Gisou van der Goot, Professor at the ETH Lausanne, who leads the project funded by Gebert Rüf Stiftung. This is the only laboratory in the world that deals intensively with this disease and explores its progression. It is no easy task for van der Goot as she says, “I feel a great responsibility to the patients. I want to give these patients some hope and, at the same time, I have to tell them that research is often extremely slow and that the development of a drug takes years and even decades.”

In recent years, van der Goot’s team has pieced together various bits of the puzzle about the origin of HF. “When we started to investigate this disease, nothing was known about its mechanism of action.”

12

“I FEEL A GREAT RESPONSIBILITY TO THE PATIENTS.“

Some cases had been described in the literature, but no information was available about the disease’s origin. Today, it is unequivocal: It is not just one single mutation that leads to this disease, but rather several occurring together that cause a faulty function of a specific protein. As a result, hyaline accumulates in the body and forms bumps.

In recent years, the team has studied exactly what causes these individual mutations and where intervention could possibly halt the process.

“For some mutations, we already have specific active ingredients which we assume could help. With others, research must test which drugs will exert an effect,” says van der Goot.

She has not regretted this decision. In the past, younger scientists were often advised not to focus on a rare disease from a scientific point of view. The problem lies particularly in the publication of results – the basis of any scientific career. Even a brilliant piece of work about a rare disease is hard to get published in prestigious journals. “I was fortunate to turn to this rare disease later in my career when my lab was already on a secure footing,” says van der Goot. In the meantime, the situation has improved somewhat, and rare diseases have achieved a higher priority.

More information about this project on page 18.

Why study a rare disease?

To investigate a rare disease is not always easy. “Many people ask me why I work on a disease that affects so few patients.” Why not explore some other condition that would help more people? Why hyaline fibromatosis?

The answer, as so often in life, is chance. Van der Goot originally worked on anthrax toxin, the protein produced by Bacillus anthracis, which causes deadly anthrax. The anthrax toxin acts on the same protein that is affected in HF patients, and this connection led to van der Goot’s contact with HF patients. “And as soon as I saw these patients for the first time, I knew that I had to do something.”

> http://vdg.epfl.ch

13

RARE DISEASES – NEW APPROACHES

“Most of all, I miss the independence.“ For many people, the years between the ages of 26 and 28 are some of the best of their lives. For Priya, 31, a Wilson‘s disease patient, they were the absolute low point. She could do virtually nothing alone, not even take a shower.

14

“MOST OF ALL, I MISS THE INDEPENDENCE.“

riya is sitting on a chair, smiling, her eyes shining and her expression open and interested. But when she gets up, her gait is stiff and awkward. Priya is suffering from Wilson’s disease, a rare genetic disorder. Her body cannot remove the excess copper that the body absorbs daily from food. Copper thus accumulates in the liver and in the brain, causing damage to these and other organs.

She found out by chance that she suffers from Wilson’s disease. “When I was 11 years old, I was rather keen on my mother’s ophthalmologist. I also wanted to be examined by him. My mother was not thrilled by the idea but I was already pretty stubborn so I prevailed,“ says Priya with a smile. During the check-up, the ophthalmologist discovered a golden brown ring around the iris, caused by copper accumulation in the eye.

After further investigation with a paediatrician and at the Children’s Hospital, the diagnosis was clear: Wilson’s disease. The doctors immediately ordered drug therapy and from then on, Priya had to refrain from eating foods having a large copper content. Even today, she finds this difficult, for example, with chocolate.

Rising copper levels Shortly before her 18th birthday, Priya had to change her physician, as she was now too old to be treated at the Children’s Hospital. At the same time, the doctors decided to replace the strong drugs she had been taking with those having fewer side effects. That this change of drugs was a mistake became clear in the ensuing years. Between

2002 and 2005, Priya completed her musical education in Hamburg.

The demanding training and stress caused her copper levels to rise.

Her physician accused Priya of not taking the drugs properly, which was indeed the case due to the side effect of severe nausea and her all-day long schedule. But above all, the new drugs were not achieving the desired effect. “In retrospect, I think I should have insisted that we switch back to the old drugs. But I trusted the doctor. I just wish he would have admitted his mistake instead of laying all the blame on me. Today, I can definitely say that I didn’t receive the best possible care,” says Priya.

Symptom exacerbation In 2005, she returned to Zurich to begin a degree in journalism. The copper values continued to increase, as did her symptoms. During her studies, she worked, moved in with her boyfriend and even appeared in a musical. She was busy but attributed her severe weight loss, fatigue, trembling and her increasingly unreadable handwriting to stress: “I sometimes just fell asleep at the kitchen table or in a lecture.

My movements looked as if I was drunk, and that’s how it felt in my head,” remembers Priya.

Three years later, when she could hardly walk, her mother brought her to Zurich University Hospital where doctors quickly recognised the gravity of the situation and instituted new treatment. Though these latest drugs worked better for her, the accumulated copper had already

15

RARE DISEASES – NEW APPROACHES

damaged the central nervous system leaving Priya with ataxia, slurred pronunciation, and cramped muscles. Rehabilitation followed with physiotherapy, muscle training and speech training. “For other people, some of the best years of their lives are between the ages of 26 and 28. For me, that period was the absolute low point. I could hardly do anything alone any more, not even take a shower, and I had to fight hard for every improvement.”

Change for the better But the efforts paid off: Today, Priya lives with her boyfriend again in a shared apartment. She has resumed her studies and should be able to complete them in 2014. She also has a new doctor. But she is no longer able to lead an independent life: Her muscles are cramped – with good days and bad days – her gait stiff, her coordination skills limited. “What I miss most of all is being self-reliant. Wherever I go, I usually need someone to accompany me. I can take the tram but only if it’s not raining, it’s not too hot and I have a lot of time. I always have to think ahead and plan. It stinks.”

On Mondays, the homecare worker comes over and helps her with the housework. In the afternoon, she goes to her student job. On other days, she works on her master’s thesis and her programme consists of strenuous physiotherapy, strength training and Feldenkrais therapy.

“Sometimes I wonder why I do it all. But the answer is quite simple: If I didn’t do it, my symptoms would be much worse.” Her family,

16

boyfriend and friends give her strength, as does the Wilson’s Disease Association Switzerland, whose members she meets with four times a year.

Don’t give up New therapies, such as gene therapy, are not yet in sight: “The fact that my disease is considered to be rare makes it particularly difficult. I know that other diseases, such as diabetes, are bad, but research is going on in these areas. With rare diseases, unfortunately, this is often not the case.

It is just not lucrative enough.”

She knows that her life will never be ”normal”. But her will to live is strong. She meets with her friends, laughs and does a lot, even excursions, when she feels up to it. In recent years, she has even learned to find a positive side to the disease: “Because of my illness, I depend on a lot of support. If I were healthy, I would not have the good fortune to spend so much time with the people who are important to me,” says Priya and her eyes light up, as always, when she speaks of her parents, her boyfriend or her friends. How much mobility and independence Priya can still win back and how the disease will develop is uncertain. But giving up is not an option: “My goal is to someday be able to walk down the stairs alone again. I know I can do this.”

Wilson’s Disease Association Switzerland > www.morbus-wilson.ch

“WE ARE COMMITTED TO THE PATIENTS.“

Is there progress in Switzerland – in research and in the political arena – in the field of rare diseases?

Slowly, but surely, medical centres of excellence are being established, a move we warmly welcome. At the University of Zurich, for example, there’s the new research priority, RaDIZ, and Lausanne and Geneva Cantonal Hospitals together with Orphanet have launched an internet platform.

With regard to research, the situation both in Switzerland and internationally lacks transparency. Although there are research projects at all levels – basic research and clinical studies – it is difficult to achieve an overview. Patients or their organisations undertake research projects and participate in raising the necessary funds, but these are often not well-publicised.

At the political level, several proposals have been submitted to the National Council and the Council of States. Arguably, the greatest progress achieved to date has been the Federal Council announcing a national strategy for rare diseases.

What is the biggest problem for patients with a rare disease?

This question does not have a universal answer. Certainly the lack of hope for a cure is hard to bear. Compounding this is that health insurers may cover none or only partial costs of treatment. Bureaucratic obstacles or lengthy lawsuits are tiring for everyone, especially for those who are ill, with possible consequences of depression and isolation.

Integration and monitoring in school and at work can be problematic and occasionally fail due to a lack of commitment.

“We are committed to the patients.“

How could the situation of patients with a rare disease be improved?

When it comes to hope for a cure then research tops the list. The more research, the closer we are to effective treatment and possibly even a cure. In addition, the gruelling administrative hurdles associated with the remuneration of diagnoses and treatments – in Switzerland, outside the canton of residence and, if necessary, abroad – should be eliminated. In addition, it would be a great help if patients with extremely rare diseases could be treated in centres of excellence. Indeed, the specialists in these diseases are just as rare as the diseases themselves.

Why do we need ProRaris?

In Switzerland, there are about one hundred patient organisations in the field of rare diseases. As most are quite small, rarely are their voices heard. As an umbrella organisation, ProRaris represents the common interests of the various groups as well as the interests of many patients with very rare diseases for whom no associations exist.

What is the role of ProRaris?

We are committed to ensuring that healthcare is provided for those people having rare diseases, and to raising awareness about this issue among the public, politicians, authorities and the relevant institutions. We ensure that patients in the health care system are treated as equal partners with valuable experience, as well as enable patients to have a say in those political decisions that affect them.

Esther Neiditsch is Managing Director of ProRaris, the Alliance of Rare Diseases Switzerland, which was founded in June 2010. ProRaris is an umbrella organisation that represents the common interests of various patient organisations as well as patients who are not allied with an association. > www.proraris.ch > www.info-maladies-rares.ch

17

RARE DISEASES – NEW APPROACHES

All Research Projects at a Glance Each year since 2009, Gebert Rüf Stiftung has supported five or six projects researching the diagnosis and treatment of rare diseases.

The Swiss university-based research teams focus on various problem areas, including respiratory, eye and immune system diseases. The treatment approaches are different – some research groups test new drugs while others apply gene therapy techniques.

More information on the projects can be found at grstiftung.ch (Area of Activity: Rare Diseases)

Facts and Figures for the Rare Diseases Programme • 338 applications with a total budget of around CHF 126 million • 26 approved projects with a total budget of CHF 10.3 million • Already more than 50 publications from the approved projects • Almost half of the projects achieved a diagnostic or therapeutic success or are already at clinical trial stage.

CALL 2013: 5 OUT OF 73 Dominant Optic Atrophy Dr. Albert Neutzner, University Hospital Basel; Funding: CHF 300,000

Dominant optic atrophy (DOA) is a form of hereditary blindness that results from the slow degeneration of retinal ganglion cells. This study focuses on the use of artificial transcription factors (ATFs) to modulate OPA1, a specific gene involved in DOA. This novel approach offers a functional cure for afflicted patients.

Cutaneous Lupus Erythematosus Prof. Dr. Jean Pieters, University of Basel; Funding: CHF 450,000

Cutaneous lupus erythematosus (CLE) is a rare, debilitating disorder that can result in permanent scarring, disfigurement and malignancy. Studies show that inhibition of the protein, coronin 1, may be an effective therapy for treating CLE. This study aims to translate these findings into a treatment procedure for the disease.

Polycystic Kidney Disease Prof. Dr. Daniel Constam, Ecole Polytechnique Fédérale de Lausanne; Funding: CHF 480,000

Polycystic kidney disease (PKD) is an inherited, life-threatening disorder characterised by fluid-filled cysts in the kidneys. In its most frequent form, cysts progressively arise along the entire nephron. The study aims to elucidate the role of bicaudal C, a protein linked to PKD.

Netherton Syndrome Dr. Matthias Schäfer, Swiss Federal Institute of Technology Zurich; Funding: CHF 380,000

Netherton syndrome is a rare disease characterised by erythroderma, atopic dermatitis and hair shaft defects. The study seeks to test the hypothesis that the activation of the Nrf2 protein is a novel approach for the treatment of Netherton Syndrome patients.

Rasmussen Encephalitis Prof. Dr. Doron Merkler, University of Geneva; Funding: CHF 490,000

Rasmussen Encephalitis (RE) is a rare but often devastating inflammatory disease of the central nervous system, characterised by epileptic seizures. Patients frequently experience intellectual decline, loss of speech and, finally, hemiparesis. The goal of this project is to provide further insights into the fairly well-understood molecular pathogenesis of RE, and open up new avenues for treatment.

18

Projekte

CALL 2012: 5 OUT OF 54

CALL 2011: 6 OUT OF 32

Pulmonary Cystic Fibrosis

Rare Colonic Diseases

Prof. Dr. Urs Jenal, University of Basel; Funding: CHF 370,000

Prof. Dr. Jean-Christophe Leroux, Swiss Federal Institute of Technology Zurich; Funding: CHF 300,000

Despite recent progress in treating patients suffering from cystic fibrosis (CF), it is not possible to eradicate chronic forms of Pseudomonas aeruginosa. The study will help to develop diagnostic tools for chronic monitoring and will lay the foundations for chemical interference with the primary cause of CF mortality.

New and more efficient pharmacological options are needed for the treatment of inflammatory bowel diseases. The study’s goal is to design novel nucleic acid drugs that can be efficiently delivered to the colon in order to decrease inflammatory reaction.

Diseases of Imprinting Prof. Dr. Didier Trono, Ecole Polytechnique Fédérale de Lausanne; Funding: CHF 400,000

Transient neonatal diabetes, Beckwith-Wiederman, SilverRussel, Angelman and Prader-Willi syndromes are rare diseases linked to defects in imprinting. The goal of this project is to decipher the mechanisms of imprinting, to expand their understanding, and ultimately, to facilitate the diagnosis and possibly the treatment of these afflictions.

Mucopolysaccharidosis

Prof. Dr. Jeffrey A. Hubbell, Ecole Polytechnique Fédérale de Lausanne; Funding: CHF 300,000

Mucopolysaccharidosis VI is a congenital enzyme deficiency that can be treated by administering galsulfase, an enzyme drug. As in many other enzyme replacement therapies, most patients develop immune reactions to the drug. This project focuses on how to utilise hepatic tolerogenic mechanisms to avoid immunological recognition.

Kidney Diseases Prof. Dr. Olivier Devuyst, University of Zurich; Funding: CHF 490,000

This project will help improve the understanding of the clinical presentation, the genetic causes and the mechanisms of uromodulin-associated kidney diseases (UAKD) and improve patient care.

Retinitis Pigmentosa Dr. Botond Roska, Friedrich Miescher Institute for Biomedical Research; Funding: CHF 500,000

Retinitis pigmentosa refers to a diverse group of rare hereditary retinal diseases that lead to incurable blindness.

The study focuses on a therapeutic gene tool that will bring optogenetic vision restoration closer to clinical application.

Dysferlinopathies Prof. Dr. Michael Sinnreich, University Hospital Basel; Funding: CHF 480,000

In this clinical study, a drug already approved for other indications is deployed in patients with muscular dystrophy.

The goal is to protect a mutated, but still fully functional, membrane repair protein from degradation, and thus contribute to membrane repair of muscle cells.

Inflammatory Bowel Disease Prof. Dr. Anne Müller, University of Zurich; Funding: CHF 190,000

This project seeks to elucidate those underlying protective mechanisms and to harness the immunomodulatory properties of H. pylori, exploiting them for the prevention and treatment of inflammatory bowel diseases using a strategy of “tolerising vaccination”.

Chronic Mucocutaneous Candidiasis Prof. Dr. Salomé Leibundgut, Swiss Federal Institute of Technology Zurich; Funding: CHF 500,000

Chronic Mucocutaneous Candidiasis (CMC) is a rare condition characterised by persistent and recurrent infections of the skin, nails and mucous membranes for which no effective treatment exists. The project seeks to improve the understanding of the molecular mechanisms that lead to CMC.

Lymphedema-Distichiasis Prof. Dr. Tatiana Petrova, Centre hospitalier universitaire vaudois (CHUV); Funding: CHF 500,000

Lymphoedema-distichiasis is characterised by swelling of the legs due to abnormal interstitial fluid transport. The disease is caused by gene mutations and the aim of this project is to find methods to reverse them.

Prader Willi Syndrom Dr. Shivendra Kishore, University of Basel; Funding: CHF 110,000

Prader Willi Syndrom (PWS) is a rare congenital disease that results from the loss of expression of genes located on chromosome 15. The project uses novel, genome-wide approaches to uncover the molecular steps leading to PWS in order to pave the way for new therapeutic strategies.

19

Rare Diseases – New Approaches 2011

Rare Disease Programme Rare Diseases – New Approaches With an annual budget of CHF 2 million, the programme promotes applied research aimed at developing and implementing innovative approaches or technologies. The goal is to improve the diagnosis and treatment of rare diseases. The call is open to researchers at Swiss universities, university hospitals, federal institutes of technology, universities of applied sciences and research institutions affiliated with Swiss universities.

Programme Objectives The programme is aimed at bridging the worlds of basic and clinical research: Projects with new approaches or technologies that focus on a clinical or diagnostic application will be supported. The project results should lead to a better understanding of the genetic, molecular and biochemical processes underlying these diseases and pave the way towards new diagnostics and new forms of treatment. The ideal project scenario would show concrete compounds and diagnostic tests from which patients suffering from a rare disease could benefit.

The focus must be on innovation, feasibility and effectiveness, while attaining high scientific and technological standards.

The programme was established in 2009 as a five-year area of activity.

Programme Managment Dr. Pascale Vonmont, Deputy Director, Gebert Rüf Stiftung, pascale.vonmont@grstiftung.ch

4 1 0 2 Call

.

2014 a rch .

M n he d i 2014 l au n c u g u s t 8 , e b l A il i l l be ct s w proje eadl i ne w r o f all nd 014 c cat io T he 2T he appl i

Masthead Gebert Rüf Stiftung, Bäumleingasse 22/4, CH-4051 Basel, tel +41 (0)61 270 88 22, info@grstiftung.ch, grstiftung.ch Concept and editorial: advocacy ag, Gebert Rüf Stiftung, Graphics: aplus, Pictures: Christoph Läser January 2014

20