Indo-American News: February 3, 2023

NRI Neuroscientist Develops First Medicine for Difficult-to-treat Epilepsy

College Station, texaS: After completing his pharmacy degree at Kakatiya University in Warangal and PhD at Panjab University in Chandigarh, India, D. Samba Reddy, PhD, RPh, now a Regents Professor in the Department of Neuroscience and Experimental Therapeutics at Texas A&M University School of Medicine, was embarking on a career teaching and researching at one of India’s leading universities. “I was happily settled,” Reddy recalled.

That is, until a letter from the U.S. National Institutes of Health (NIH) arrived in his mailbox in 1998 and changed his career trajectory forever. Michael Rogawski, MD, PhD, one of the top scientists at the NIH, had invited Reddy to his lab as a visiting scientist.

Reddy had never heard of the NIH, so he reached out to his PhD mentor S.K. Kulkarni, PhD, for advice. His mentor told him that the best research happens at the NIH, and that he should take advantage of the opportunity. So, Reddy decided to come to the NIH and stay for a year or two. That was nearly 24 years ago.

Today, Reddy is a Regents professor of Neuroscience and Experimental Therapeutics, Engineering Medicine, Biomedical Engineering and Veterinary Integrative Biosciences at Texas A&M University. He is the founding director of Texas A&M Institute of Pharmacology and Neurotherapeutics. His research focuses on pharmaceutical therapies for epilepsy. He has spent much of his career studying ganaxolone, a synthetic neurosteroid with potential to treat specific kinds of epilepsy.

Reddy’s body of research on ganaxolone showed the compound was successful, allowing ganaxolone to be tested in patients during clinical trials. In March 2022, the U.S. Food and Drug Administration (FDA) approved ganaxolone to treat CDKL5deficient epilepsy, a rare type of refractory epilepsy caused by mutations in the CDLK5 gene. Ganaxolone is the first drug to be approved to treat this condition, earning it a first-in-class designation.

“When I packed my two bags to come to the United States from India, little did I know that I would be part of the process of developing a drug that can be helpful to patients worldwide,” Reddy said. “It was just the beginning.”

Forging the foundation of neurosteroids

Reddy has spent his career studying neurosteroids, which are compounds that are synthesized in the brain and influence brain functions and mood. The brain continuously makes neurosteroids, as they quickly degrade after being used. Although they look chemically similar to steroid hormones, such as testosterone and estrogen, neurosteroids serve significantly different physiological functions.

“They promote more well-being,” Reddy said. “We feel good when they are in the brain—like no anxiety—and when we feel good, there’s

no depression. Neurosteroids control the way your brain reacts and dampen neuronal network dysfunction.”

While obtaining his PhD, Reddy studied how neurosteroids differ in expression between men and women. He published 14 papers on the subject, which is nearly unheard of for a graduate student. His plethora of work on a topic that few researchers study drew scientists at the NIH to recruit Reddy.

Once Reddy got to the NIH, he continued studying neurosteroids, but his work shifted in a slightly new direction. “The goal was to study the role of neurosteroids in brain diseases and what kind of diseases are affected by neurosteroids—either from lack of neurosteroids or neurosteroid fluctuations,” Reddy said.

Reddy homed in on women’s brain health. He started studying the role of neurosteroids in catamenial epilepsy, in which women experience seizures at increased rates during specific phases of their menstrual cycle. Traditional antiepileptic medications are not overly effective at controlling this condition, and so the disease is hard to treat. But Reddy saw a potential solution: neurosteroids.

“We reasoned: ‘Why don’t we just give small amounts of neurosteroids exogenously, just giving them an injection or a tablet?’” Reddy recalled. And it worked. Reddy had correctly hypothesized that these women’s seizures were caused by a neurosteroid deficiency and that giving them neurosteroids could treat the problem. Reddy and his lab added to the growing awareness of this treatment strategy, which is called neurosteroid replacement therapy.

“When undergoing neurosteroid deficiency, the brain is in a hungry state,” Reddy said. “You don’t need that much of a neurosteroid to activate the brain function.” And the neurosteroid Reddy replaced to activate the brain function in women with catamenial epilepsy? Ganaxolone.

to determine the mechanisms behind neurosteroids, including ganaxolone. Determining ganaxolone’s mechanism took several years, but Reddy and his lab demonstrated that it binds to two types of receptors in the brain: synaptic receptors, which exist on the membrane of neurons, and extrasynaptic GABA-A receptors, which bind and release molecules outside a neuron.

Reddy found that when ganaxolone binds an extrasynaptic GABA-A receptor, the effect is more powerful and lasts longer.

tive synthetic neurosteroids. These molecules are considered “superganaxolones” because they work better than ganaxolone.

Once Reddy figured out ganaxolone’s mechanism and structure, he had the necessary information to start designing and synthesizing his own neurosteroids that overcame the limitations of the synthetic ganaxolone and other similar naturally occurring neurosteroids. He has currently filed patents for more than 20 synthetic neurosteroids that he has designed.

Persevering through research roadblocks in developing brain medicines

Still, it would take more than two more decades of research and several more experiments until ganaxolone was approved for major clinical use. Reddy left the NIH in 2002 to accept a faculty position at North Carolina State University. There, he continued his work on ganaxolone, as he needed to provide more evidence of the drug’s efficacy before it could be clinically implemented.

Reddy was not deterred by others’ skepticism. “Skepticism is a good thing,” he said. “Doubting some science is good that way because then you get robust evidence, and you do more research.”

Reddy continued with his research, receiving millions of dollars in funding from the NIH and other sources. He remained one of only a few individuals looking at the effects of neurosteroids and their role in the brain and seizures. Big companies had been looking at the potential of neurosteroids to treat neurological conditions, but they had given up and abandoned the research. But Reddy kept going. “Time will answer everything,” he said. “So, I thought, ‘Okay, I’ll do research whether anything comes out or not.’”

Still, there was a problem. Reddy—and the few others working on neurosteroids—did not know much about the biology of how neurosteroids worked in the brain. Even if ganaxolone, which is a slightly modified synthetic version of a neurosteroid that naturally occurs in the human body called allopregnanolone, and other neurosteroids were showing promise in early experiments with patients, researchers could not give the drugs without understanding how they worked. So, in 2008, Reddy accepted a faculty position at the Texas A&M School of Medicine to gain access to resources that would allow him to push his research to the next level.

Once at Texas A&M, Reddy used additional techniques and models

Reddy’s research was crucial to showing ganaxolone’s effectiveness: work from his lab identified the target molecule in the brain and validated ganaxolone’s effectiveness. Then clinical trials showed the drug was indeed both safe and successful in patients with epilepsy.

Finally, in March 2022, ganaxolone (as brand name Ztalmy) was approved by the FDA for clinical use in CDKL5-deficient epilepsy. “It is a lifetime achievement,” Reddy said. “This is opening gates to things that we could not even imagine when we started this research.”

Achievements and looking to the future

The crowning achievement for pharmacology researchers is designing a safe, effective drug approved by the FDA, a task that is only rarely accomplished. In just 24 years of research, Reddy contributed to not one but two FDA-approved medications. Ganaxolone joins brexanolone (an injectable version of the neurosteroid allopregnanolone), which in 2019, became the first FDAapproved neurosteroid and the only FDA-approved treatment for postpartum depression, a serious mental health condition in women after childbirth.

“The greatest goal in research is to provide transformational outcomes—seeing the product you helped make on shelves in the pharmacy and benefiting people,” Reddy said.

Reddy is not done yet either. After his success with ganaxolone, Reddy is determined to do more for those with other types of seizures. He is currently working on several projects that may help more people affected by epilepsy, including posttraumatic epilepsy that occurs after traumatic brain injury, which affects many soldiers who have been in combat.

“It totally changes the person’s perspective, receiving a diagnosis of epilepsy,” Reddy said. “If their epilepsy cannot be treated, they can’t drive, they can’t enlist in the army, they can’t fly airplanes, they can’t operate any machinery. It takes away their freedom.”

Reddy is determined to do what he can to help people with epilepsy get their autonomy back. For one, he has developed even more effec-

“By designing synthetic neurosteroids, we overcame issues that limited the first-generation products,” he said. “Compounds can stay longer in the body, there are no hormonal side effects, and then we can give the compound via once daily or twice daily administration.”

And that’s not the only thing Reddy is working on. He is also trying to expand the clinical uses of ganaxolone and related neurosteroids to include more types of epilepsy. Plus, with the support of a $51 million Biomedical Advanced Research and Development Authority (BARDA) grant to a collaboration of institutions and companies, a phase 3 clinical study is examining whether ganaxolone can treat status epilepticus, which is a seizure that exceeds five minutes and involves a loss of consciousness, which can often lead to serious brain injury or death. Status epilepticus is a lifethreatening condition that occurs more commonly in people exposed to pesticides or soldiers encountering chemical weapons. Currently, there is little that military medics can do for soldiers who develop status epilepticus. Reddy said he hopes that, if research continues to confirm its success, ganaxolone will become a life-saving staple in medical kits around the world.

“This product will become an antidote in every soldier’s backpack. And then it will be available in every ambulance,” Reddy said. “And as soon as you go to a patient, if an accident or something has happened and is he seizing, you give him a low-stress shot. That was the idea—to help both soldiers and help civilians with this neurosteroid treatment.”

These real-life applications that help patients are what drew Reddy to pharmacology in the first place, and they motivate Reddy to continue pushing the boundaries of neurosteroids and treatments for epilepsy—even if it means he has to stay in the United States, thousands of miles away from his family in India.

“My work is making a difference to patients. That sustains me,” he said. “So that’s the reason why I hang around and want to stay here and do as much as I can.”

Reddy’s research was funded by the National Institute of Neurological Disorders and Stroke, part of the U.S. National Institutes of Health, and partly supported by the U.S. Department of Defense.

India’s 74th Republic Day Celebrated with Enthusiasm throughout Houston

India House hosted its annual Republic Day flag hoisting on January 26.

Consul General Aseem Mahajan (right) hosted an evening reception with attendance by local Indo-American community and elected officials, including Houston Mayor Sylvestor Turner and FB County Judge KP George.

GSH held a flag hoisting on Thursday as well as the ICC R-day fair on Sunday.

First order of the day was flag hoisting at the Indian Consulate.

Job Posting

Job ID 10038386; Location Houston, Texas

KTRK-TV, an ABC-owned station in Houston, TX, has an opening for a full-time Non-Linear News Editor

Responsibilities

• Editing video for daily newscasts

• Importing and exporting of video content

• Establishing live signals for broadcast and video intake

• Content creation from various file types and video formats

Basic Qualifications

• The ability to work under tight deadlines, multi-task, and prioritize assignments

• Team player with exceptional work ethic and technical troubleshooting skills

• Knowledge of the digital newsroom and understanding of the digital workflow for broadcast and streaming newscasts and server-based digital media workflow

• Experience with Adobe Premiere Pro, Dalet Galaxy, and live signal intake

Required Qualifications

• Minimum 1 year experience

• Demonstrate good news judgment

• Experience in editing on non-linear systems

• Editing in tight deadline situations, being creative, precise and being able to work fast

• Flexibility to work any shift/any day including weekends and holidays and as business dictates in extended breaking news scenarios

Required Education

• High School Diploma or equivalency

Preferred Education

• Bachelor’s

Interested candidates apply via Disneycareers.com

About ABC Owned TV Stations: Comprised of the Company’s international business units and various direct-to-consumer streaming services, Disney Media & Entertainment Distribution (DMED) aligns technology, media distribution and advertising sales into a single business segment to create and deliver personalized entertainment experiences to consumers around the world.

About The Walt Disney Company:

The Walt Disney Company, together with its subsidiaries and affiliates, is a leading diversified international family entertainment and media enterprise with the following business segments: media networks, parks and resorts, studio entertainment, consumer products and interactive media. From humble beginnings as a cartoon studio in the 1920s to its preeminent name in the entertainment industry today, Disney proudly continues its legacy of creating world-class stories and experiences for every member of the family. Disney’s stories, characters and experiences reach consumers and guests from every corner of the globe. With operations in more than 40 countries, our employees and cast members work together to create entertainment experiences that are both universally and locally cherished.

This position is with KTRK Television, Inc, which is part of a business we call ABC Owned TV Stations.

KTRK Television, Inc is an equal opportunity employer. Applicants will receive consideration for employment without regard to race, color, religion, sex, national origin, sexual orientation, gender identity, disability or protected veteran status. Disney fosters a business culture where ideas and decisions from all people help us grow, innovate, create the best stories and be relevant in a rapidly changing world.

Job Posting

KTRK/ABC13 is looking for a leader who can help grow and develop our staff of news photojournalists.

This person will manage our team of 15-20 photographers that staff our operation 24/7 while still shooting in the field from time to time.

We are looking for someone who can coach our team and bring our visual storytelling to the next level.

Responsibilities

• Regular field newsgathering for multiple newscasts

• Managing our team of photojournalists

• Would manage ENG purchasing

• Evaluation of new and emerging technology

• Best practices and policy implementation

Basic Qualifications

• Minimum 5 years’ experience

• Experience shooting in a news environment

• Willing to work any day/any shift

• Experience with the Panasonic brand of cameras and lenses

• Experience with field and interview lighting

• Editing with the Premiere Pro or similar editing suite

Required Education

• High School Diploma

Preferred Education

• BS, Journalism/Communications or similar

Interested candidates apply via Disneycareers.com

About ABC Owned TV Stations:

Comprised of the Company’s international business units and various direct-to-consumer streaming services, Disney Media & Entertainment Distribution (DMED) aligns technology, media distribution and advertising sales into a single business segment to create and deliver personalized entertainment experiences to consumers around the world.

About The Walt Disney Company:

The Walt Disney Company, together with its subsidiaries and affiliates, is a leading diversified international family entertainment and media enterprise with the following business segments: media networks, parks and resorts, studio entertainment, consumer products and interactive media. From humble beginnings as a cartoon studio in the 1920s to its preeminent name in the entertainment industry today, Disney proudly continues its legacy of creating world-class stories and experiences for every member of the family. Disney’s stories, characters and experiences reach consumers and guests from every corner of the globe. With operations in more than 40 countries, our employees and cast members work together to create entertainment experiences that are both universally and locally cherished.

This position is with KTRK Television, Inc, which is part of a business we call ABC Owned TV Stations.

KTRK Television, Inc is an equal opportunity employer. Applicants will receive consideration for employment without regard to race, color, religion, sex, national origin, sexual orientation, gender identity, disability or protected veteran status. Disney fosters a business culture where ideas and decisions from all people help us grow, innovate, create the best stories and be relevant in a rapidly changing world.

YLDP Session with CEO of ‘Black Girls Do Engineer’ EGMH Observance of Martyrs Day

‘Houston

Landing’: A New Digital News Platform

HouSton: Houston Landing – a new digital news platform that will provide essential and independent journalism – was launched Feb. 1, powered by a team of veteran journalists passionate about accountability reporting and telling stories that reflect the region’s diversity.

With more than $20 million pledged before its launch, Houston Landing is one of the most wellfunded projects in a burgeoning industry of nonprofit news sites nationwide. The Landing begins with a newsletter at www.houston-

landing.org and will evolve into a full website later this spring.

Houston Landing’s mission is to strengthen democracy and improve the lives of all Houstonians one story at a time.

The Landing’s content will be free with no paywalls or subscription fees to ensure that its high-quality journalism reaches as many people as possible. It will also allow other news media to freely republish its content.

The project will be led by Chief Executive Officer Peter Bhatia, who helmed newsrooms that

Consulate General of India Houston

JOB VACANCY

The Consulate General of India, Houston invites application for the post of Chauffeur cum Messenger from the applicants who are either US citizens or permanent residents, residents with valid appropriate visa or valid work permit.

Interested candidates may send their application and resume along with all supporting documents (for educational qualification/ passports/ visa/work permit etc.) latest by February 12, 2023:

• by email to: hoc .houston@mea.gov.in

• or by post to:

Head of Chancery

Consulate General of India

4300 Scotland Street, Houston, Texas 77007

For further details visit the Consulate website: www.cgihouston.gov.in

have won 10 Pulitzer Prizes, and Editor-in-Chief Mizanur Rahman, who has spent the past 15 years in senior roles at the Houston Chronicle.

They are assembling a team of journalists to shine a light on injustices and solutions, give voice to the voiceless, hold the powerful to account, deepen understanding, elevate discourse and serve as a catalyst for positive change.

Funded with seed investment from three leading local philanthropies – the Houston Endowment, Arnold Ventures and the Kinder Foundation – Houston Landing was born out of a twoyear study spearheaded by the American Journalism Project that found many Houstonians do not feel they have access to a trusted source for deeply reported stories that impact their daily lives.

It will represent and reflect the region’s informational needs by tirelessly listening to its communities.

YLDP Houston Students held a session with motivational speaker Kara Branch, Founder and CEO of “Black Girls Do Engineer” Corporation. It was a fun-filled, interactive and great learning session for the YLDP Students.

CG Aseem Mahajan pays homage at Mahatma Gandhi statue in Hermann Park on the observance of Martyrs Day on Jan. 30, which commemorates Gandhi’s assassination in 1948.

Indian Film Festival of Houston Celebrates Its 15th Anniversary

HouSton: The Annual Indian Film Festival of Houston (IFFH), begun by its Founder and Executive Director Sutapa Ghosh in 2009, keeps getting better and better. This quality event screens features, shorts, and documentary film with Q & A sessions with filmmakers. There are bonuses as well. No wonder IFFH was voted as the “Best Film Festival of Houston” by the Houston Press. The Houston Chronicle has also listed IFFH as one of the Top 4 events in the first quarter of this year.

Partnering with the Asia Society Texas Center proved to be a beneficial collaboration for both non-profit organizations. Films are shown in the state-of-the art Brown Theater, and the beautiful building lends itself to having live entertainment, as well as cocktail and food receptions. Celebrating its 15th anniversary, this year IFFH will add a black-tie sit-down dinner along with awards given for the best films in the three categories.

Several filmmakers—directors and actors—will be present, along with Consuls General, Vice Consuls and other dignitaries. The audience includes attendees from Houston, surrounding cities and states, and even other parts of the world. People have come from as far away as Mexico, France, Germany, Japan, Korea, Argentina, and Morocco, to name a few, as the festival’s reputation has spread globally.

IFFH is an internationally-recognized competitive film festival.

Several of the productions shown here have gone on to win other international awards at the Oscars, Sundance, Toronto, Cannes, Ber-

lin, and Busan.

Audiences are in for a treat, as the selections this year include the World Premiere of Tikdam, a

feature film set in a small town. It dwells on lessons learned along the way when the father migrates with his children to a larger city

where he hopes to earn a living.

The two short films are also World Premieres. Preet is a psychological drama about newlywed who escapes her sexually abusive past and finds refuge in New York City through a childhood friend. It showcases the trauma and mental turmoil of a survivor in society.

The Counterpart has a new twist on the story of two childhood friends who fall in love with the same girl. Betrayal by one of them causes a major psychological breakdown of the other who leaves town. He returns two years later and gradually reveals his true intentions.

The second feature film is The Storyteller, based on the character “Uncle Tarina” who appears in short stories by the incomparable Indian filmmaker Satyajit Ray. After retiring from being a printer, Tarina answers an advertisement calling for a storyteller to go to the opposite side of India. Thinking that it is for a job in a school, he’s surprised to find that his employer is a wealthy businessman who has insomnia and wants Tarina to tell stories to help him fall asleep. What happens six months later changes both the story and its teller. Two outstanding documentaries round out the selections for this milestone anniversary year.

You may see a listing of this year’s films at www.iffhinc.org. We invite you to join us for film screenings Thursday and Friday, February 23-24 from 4:00 pm9:00 pm. and for the Awards Dinner from 6:00 pm-9:00 pm on Saturday, February 25, 2023.

Stills from the movie Tikdam (top) and The Storyteller

‘Gandhi Godse Ek Yudh’: Naïve, Insidious

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By SHuBHra gupta

Looking back at historical figures with the benefit of hindsight can be an interesting exercise. Rajkumar Santoshi posits a question in his ‘Gandhi Godse Ek Yudh’: what if Godse’s lethal attack on the Mahatma had failed? What if the two were given untrammeled time to converse with each other? Would there have been a dilution of ideology, or change of heart on the part of Nathuram Godse, one of the most reviled names in modern history?

But Santoshi’s attempt at revisionism is marred by trying to play it both ways, and falling between the planks. What we get is a series of equally weighted back-and-forth cuts between Gandhi (Deepak Antani) and Godse (Chinmay Mandlekar), as they go about their business: the former trying to douse the inflamed passions of people and a country on the verge of Partition, the latter getting more and more enraged by the escalating situation. A scene of conciliation following a scene of agitation, in a loop, puts into place false equivalence, both naïve and insidious.

Antani’s playing of Gandhi is impressive. In one instance, he gets the toothless laughter just right, apart from pulling off the physical appearance of dhotiglasses-charkha, and his smiling visage, ever ready to turn the other cheek.

Mandlekar is made to constantly rail and

flare his nostrils, turning him into a uni-dimensional hot-head who keeps justifying the murder of one of the greatest pacifists the world has known, by denouncing him as the man who didn’t hold the interests of the Hindu community above all, and who forced a love of Muslims down reluctant throats.

One of the film’s ideas is to debunk the kind of myths which have been gaining currency on WhatsApp groups, that he agreed to hand over precious crores to Pakistan. Gandhi is shown lecturing Godse on the error of his ways: ‘nihaththon pe vaar karna koi dharm nahin sikhata’ (no religion advocates aiming at defenseless people). Which is all very well, but there’s no weight to this and a lot more that the Mahatma, shown to be increasingly isolated from the actual functioning of the newly-formed government, tries to impart to the man he has ‘for-

given’.

What if fictional forgiveness is extrapolated and turned into fact in these post-truth times? People in the theatre were laughing at Godse proclaiming about how while people are dying, Gandhi is busy drinking ‘bakri ka doodh’: this kind coarseness goes down easier than anodyne lectures on ‘ekta, vividhta, vishaalta’ of the country.

The film does try and interrogate Gandhi’s strange ideas on love and celibacy through the device of a young girl (Tanisha Santoshi, the director’s daughter) who is forced to choose between serving the nation and a suitable young man (Anuj Saini). But it is clunkily done, as is the film.

Cast: Deepak Antani, Chinmay Mandlekar, Tanisha Santoshi, Anuj Saini Director: Rajkumar Santosh

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Composer: A.R. Rahman

Rating: 1.5 stars

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