Metabolic Matters (Issue 5)

MAY 2022

YOUR MONTHLY MSUK MAGAZINE

Metabolic Matters

New horizons for whole genome sequencing

CONTENTS

FOCUS ON: WHOLE GENOME SEQUENCING (PAGE 4) NEW DEVELOPMENTS: THE EXPANSION OF WHOLE GENOME SEQUENCING IN THE UK (PAGE 5) THE FUTURE OF MEDICINE: GENE THERAPY AND IMDS (PAGES 6-7) KNOW YOUR IMD: HYPOPHOSPHATASIA (PAGES 8-9) WE WORK FOR YOU (PAGES 10-11) TRAVEL INSURANCE SURVEY: THE RESULTS (PAGES 1213) BEACON FOR RARE DISEASE: THE RARE DISEASE SHOWCASE (PAGES 14-15) THE LONDON MARATHON (PAGE 16) GET INVOLVED (PAGE 17)

Focus on: Whole Genome Sequencing (WGS)

What is a genome?

The complete set of genes or genetic material present in a cell or organism. Each genome contains all of the information needed to build that organism and allow it to grow and develop.

What is Whole Genome Sequencing (WGS)?

A comprehensive method for analysing entire genomes.

(Genomic information has been instrumental in identifying inherited disorders).

How does WGS work?

Unlike other genetic tests that only look at a few genes, whole genome sequencing looks at all your genes in one go.

How is the genome tested?

The whole genome sequencing test is usually carried out on a blood sample, which is sent to a genomic testing laboratory to be analysed.

Why does it matter to me?

Understanding the genomics of rare disease can help doctors pinpoint the cause of undiagnosed disorders, helping families avoid years of hospital visits and unnecessary tests.

New Developments: The expansion of whole genome sequencing in the UK In September 2020, the UK government published Genome UK – the future of healthcare, setting out the government’s 10-year strategy to create the most advanced genomic healthcare system in the world, delivering better health outcomes at a lower cost.

The role of NHS England and NHS Improvement is to enable the NHS to harness the power of genomic technology and science to improve the health of our population and deliver on the commitments in the NHS Long Term Plan.

To be the first national health care system to offer whole genome sequencing as part of routine care.

To sequence 500,000 whole genomes by 2023/24 and help transform healthcare for maximum patient benefit, including for all children with cancer or children who are seriously ill with a likely genetic disorder.

Extended access to molecular diagnostics and offer genomic testing routinely to all people with cancer.

Early detection and treatment of high-risk conditions including expanding genomic testing for Familial Hypocholesterolaemia.

Linking and correlating genomic data to help provide new treatments, diagnostic approaches and help patients make informed decisions about their care.

Information taken from the NHS Genomic Medicine Service*

Key points for the NHS Long Term Plan

The future of medicine: Gene therapy and IMDs

Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease.

Genes contain your DNA — the code that controls much of your body's form and function, and in most Inherited Metabolic Disorders, faulty genes results in an enzyme deficiency.

How does gene therapy work?

Gene therapy is the transfer or editing of a genetic material to cure a disease.

Depending on the delivery strategy chosen, gene therapy can be performed in vivo (inside the body) or ex vivo (outside the body) with integrating (i.e. permanent modification of the host genome) or non-integrating (e.g. through viral vectors which are modified versions of a virus that is different from the virus being targeted to deliver important instructions to our cells.

What do you mean...In vivo?

In vivo gene therapy refers to the injection of a vector encoding the gene of interest or molecular tools for gene editing, directly into a tissue or into the bloodstream to generate therapeutic outcomes in specific or multiple organs.

What do you mean...Ex vivo?

Ex vivo gene therapy involves manipulation of a target cell population outside of the body, often as part of stem cell therapies, in which a patient’s own cells are genetically modified with gene editing or gene supplementation and then inserted back into the patient

What are the benefits?

Gene therapy aims to address the non-functioning gene and provide a long-term treatment benefit with potentially just one dose.

This means people living with an IMD could receive gene therapy once and have all symptoms removed permanently*, allowing for a better quality of life, whilst also ensuring people can live longer.

Okay...sounds good but what are the potential negative effects?

Unwanted immune system reaction: This may cause inflammation and, in severe cases, organ failure.

Targeting the wrong cells: If this happens, healthy cells may be damaged, causing other illness or diseases, such as cancer.

Infection caused by the virus: It's possible that once introduced into the body, the viruses may recover their original ability to cause disease.

Possibility of causing a tumour: If the new genes get inserted in the wrong spot in your DNA, there is a chance that the insertion might lead to tumour formation. *Despite these potential negative outcomes, gene therapy undergoes rigorous testing before becoming available, meaning any concerns for safety are monitored and addressed accordingly.

Know your IMD: Hypophosphatasia (HPP) What is it?

Hypophosphatasia (HPP) is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralisation, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.

Symptoms Hypophosphatasia weakens and softens the bones, causing skeletal abnormalities Affected infants are born with short limbs, an abnormally shaped chest, and soft skull bones. Perinatal HPP blocks skeletal mineralisation, including in the womb which lead to deformities, with some pregnancies ending in stillbirth, whilst some affected newborns survive for several days, but if untreated die from respiratory failure due to deformities and weakness of the chest.

Additional complications in infancy include poor feeding and a failure to gain weight, respiratory problems, and high levels of calcium in the blood, which can lead to recurrent vomiting and kidney problems. These complications are lifethreatening in some cases.

The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Some children lose "baby" teeth in infancy or early childhood, this is known as odontohypophosphatasia.

Adult forms of hypophosphatasia are characterised by fatigue, reduced mobility and a softening of the bones known as osteomalacia. Some adults experience recurrent fractures in the foot and thigh bones which can lead to chronic pain.

Affected adults may lose their secondary (adult) teeth prematurely and are at increased risk for joint pain and inflammation.

How is it treated?

Strensiq is used to treat perinatal, infantile, and juvenile onset HPP and managed access agreements have provided limited cover to UK adults.

Treatment is symptomatic and supportive. Some patients who have paediatriconset forms may also be able to access Strensiq on the managed access agreement as part of NICE appraisal (For more on the managed access agreement for Strensiq, visit the following link: https://bit.ly/3MVPmq8) Other treatments target specific symptoms and complications.

-Non-steroidal anti-inflammatory drugs to treat bone and joint pain -Vitamin B6 to help to control seizures in severely affected infants -Regular dental care beginning early on -Physical and occupational therapy -Surgery -Metal rod insertion to strengthen bones -Orthotic braces

Metabolic Support UK strongly supports our HPP community, continually advocating for continued access to Strensiq, and supporting individuals throughout every other aspect to ensure that despite diagnosis, they have the best quality of life possible.

To learn more about HPP, email jonathan@metabolicsupportuk.org for a copy of our HPP insight presentation.

We work for you This month seems to have flown by, perhaps because of all the bank holidays! We have really enjoyed chatting to many members of our community this month, either in person, via video or at our fortnightly coffee and chat sessions. Our CEO Kirsty has been out and about this month, meeting our partners and advocating for our community.

We were delighted to receive an invite to the MPS Society’s 40th anniversary event earlier this month and we offer our heartfelt congratulations to our colleagues at the MPS Society as they celebrate their 40th anniversary this year. Our fundraisers have also been busy this month, arranging or taking part in events and raising vital awareness. A big thanks to all our fundraisers and supporters, your support really does make a difference. To find out what the MSUK team have been up to this month, check out our updates below.

Advocating for the PH1 community This month, the National Institute of Care and Excellence (NICE) appraised the treatment Lumasiran. Our Head of Insight Jess and patient Ambassador Becky attended the committee meeting and shared their experiences of the challenges of living with PH1 and the benefits and challenges of the treatment being appraised.

Unfortunately, NICE decided not to recommend Lumasiran and therefore the appraisal process has now entered public consultation.

This means, anyone living with or interested in PH1 and Lumasiran can take part in the public consultation and share their feedback to NICE. Jess and Becky will be preparing their own responses and will be taking part in a second committee meeting during the summer to review NICE’s decision. To take part in the appraisal please visit the following site: https://www.nice.org.uk/consultations/1739/1/committee-discussion.

Addressing IMD/Travel insurance challenges It was recently raised to us that obtaining travel insurance is increasingly becoming a concerning issue for those with an IMD. At the beginning of May we launched a survey to capture key data on the extent of this issue within our communities. We received a fantastic response and will be sharing our findings with you shortly.

Following the survey, we have been in discussions with leaders at several travel insurers and medical screening companies to highlight key issues and themes, advocating for better access to travel insurance for those living with IMD’s. Our discussions are ongoing, and we will continue to keep you updated.

Working with Genomics England In 2023 Genomics England will be launching a ‘Whole Genome Sequencing’ programme. For more information on Whole Genome Sequencing check out our article on page 4. Genomics England are running a series of workshops to discuss the principles of new-born screening and how to decide which conditions are screened for. We have been working with Genomics England to ensure that the voice of those with an IMD is heard and included when it comes to making decisions regarding the future of new-born screening of rare and genetic conditions. The workshops will take place on 8th and 11th June, contact Jak for more information jak@metabolicsupportuk.org.

Joining the Wales Cross-Party Group This month we joined the Wales Cross-Party Group for Rare, Genetic and Undiagnosed Conditions to hear about the upcoming launch of the Wales Rare Disease Action Plan. Many of the actions outlined in the plan are designed to improve the outcomes of those with an Inherited Metabolic Disorder, whether that be through reducing the time to diagnosis, improving co-ordination of care or enhancing access to treatments. We are currently reviewing each of the plans and within the coming months we will share some bite-sized information on each of the plans and what this means for our community.

Supporting You This month we have received an increasing number of enquiries from members from our international communities, both expats and those moving to the UK. We have supported some of you to understand and navigate new healthcare systems including accessing treatment and care pathways in the UK and abroad. Lots of our community are beginning to think about travelling during the next few months.

We have received many enquiries regarding advice when travelling with an IMD and how to access metabolic medical care whilst on holiday. We continue to provide ongoing support to our online communities and are currently working with the UCD community and key stakeholders to address and resolve issues with specific treatments.

Thanks to everyone who has contacted us this month if you are seeking support or information please contact us.

Calling: 0845 241 2173 E-mailing: contact@metabolicsupportuk.org Social Media Completing our online contact form: https://www.metabolicsupportuk.org/contact-us/

Travel Insurance Survey: The Results Living with an IMD does not mean a life without travel With 54% of those living with or caring for someone with an IMD having travelled abroad 3 or more times over last five years.

But getting travel insurance is a struggle and a worry for many

60%

Have experienced difficulties in getting travel insurance to cover

73%

Worry about getting travel insurance to cover the IMD they are living with.

69%

Said the thought of getting travel insurance puts them off travelling.

“The only provider that did cover the condition by name has removed it. No other insurer recognised the condition.”

A parent/carer to a person living with an IMD

Our communities have noticed the situation changing for the worse

59% Who have looked for travel insurance in past 2 years have said it’s become more difficult to find cover or can’t find cover at all.

44% Say it’s got significantly more expensive

57% Say level of cover provided has worsened.

"I have been on holiday 3 times pre Covid and while some are very dear we have had cover, but not since Covid.”

A parent/carer to a person living with an IMD

Here’s who our communities said they would recommend Top recommended providers StaySure, Post Office, AllClear, Cover For You Other recommended providers Asda, Avanti, Boots, Holiday Extras, Insure and Go, Just Travel, SAGA, Explorer, Sainsbury’s, Free Spirit, Worldwide Insure, Freedom, Good to Go About this survey In April 2022, 48 people living with or a parent/caregiver of someone with an IMD took part in our survey about travel insurance, representing 15 IMDs.

What we're doing Holidays are important! Everyone needs a break and that's why we're speaking to insurers and partner organisations to ensure equitable access to travel insurance for you!

We're working to ensure your conditions are covered and that you're not paying too much to go on your well deserved break through educating and informing providers about IMDs.

Beacon's in-person Cambridge Rare Disease Showcase Tickets are now available for Beacon’s in-person Cambridge Rare Disease Showcase – an official One Nucleus ON Helix 22 satellite event!

Come celebrate the innovative rare disease projects taking place across Cambridge and the wider world at The Clayton Hotel in Cambridge on 6th July from 6:30 to 9:00pm.

The Cambridge Rare Disease Showcase is Beacon’s first in-person event since 2020, so register now to enjoy ample face-to-face networking opportunities, complimentary food and refreshments and a full night of exciting lightning talks!

If you think that you can #BeatTheBell, submit a lightning talk proposal when registering for the Rare Disease Showcase to discuss your rare disease registry, initiative or story. Share how you’re building connections within the rare disease space and highlight your innovative programmes, no matter how big or how small. Take the stage to reveal how you’re driving change for those living with rare disease.

Lightning talk proposals must be submitted by 6 June

Beacon’s Showcase is essential to breaking down barriers between patient groups, healthcare professionals, industry, academia, researchers and students. Incredible progress has already been made in 2022 by patient groups, which Beacon summarises on its website.

Register now for FREE (Patients, patient groups, students and charities) to form connections and collaborations and join this unstoppable movement that’s bringing real change to those living with rare disease.

Connect with the community to ensure that no one walks their rare journey alone. https://www.rarebeacon.org/rare-disease-showcase/ The Cambridge Rare Disease Showcase 18:30 – 21:00, 6th July 2022 The Clayton Hotel, Cambridge, CB1 2FB

The London Marathon The London Marathon is our biggest community fundraiser, providing crucial contributions towards our key services to ensure anyone affected by an IMD is seen, heard and supported.

So how would you like to take part in The London Marathon for us this year? Fill out the application form at the link below and make life better for those affected by IMDs. Application form

Get involved Metabolic Support UK couldn't exist without you and we aim to do even more in the future to ensure anyone affected by an Inherited Metabolic Disorder is seen, heard and supported.

To enable us to keep working for you why not: Donate Fundraise Volunteer