Spinal Muscular Atrophy (SMA) is not exactly a rare condition. One in 45 of us is a carrier of the mutant gene that causes it. We would need two copies for the muscle weakness to manifest. In Abhinand's case, both his parents happened to be carriers, and their son inherited both of their faulty copies. This happens once in 10,000 births. "I started talking when I was just 13 months old... I was a really smart kid, I suppose," Abhinand said with a smile. "But I did not hit the other milestones – crawling, standing up, walking – and my parents got worried. They took me to a neurologist and that's when they found out something was wrong with me."
Thirty years ago, human genetics were nowhere as well-studied as it is today, so the family did not receive a very clear diagnosis. They were told that Abhinand likely had Duchenne Muscular Dystrophy or SMA. It was only 10 years later that it was confirmed that he had SMA Type-3, typically considered less severe than Type 1 and 2 which manifest earlier in a child's life. However, Abhinand’s Type-3 is not so typical.
The key to our muscles working lies in a protein our body produces called survival motor neuron protein (SMN). Without enough SMN, our muscles would wither away resulting in decreased mobility as well as difficulties in breathing, swallowing and other activities that involve muscular movement. A gene called smn1 ensures that we have enough SMN. People with SMA have a mutation in smn1. Many of them receive some relief from another 'back-up' gene called smn2, which also produces SMN but not as effectively. All of us have 2 to 8 copies of this substitute smn2 gene. Exactly how many copies of smn2 we have doesn’t really matter if our smn1 is working well, but for those with SMA this could be the difference between mild and severe. The more copies of smn2 genes they have, the less severe their symptoms. Most SMA type-3 patients have 3 or more copies of sma2. Abhinand, however, doesn’t. "It's a very, very rare thing, but I'm one of the 1% of Type-3 people to have just two copies of smn2," he says, referring to himself good-humouredly as a 'genetic wonder'.
This aspect of Abhinand’s genome is probably why his symptoms were more severe than typical SMA Type-3 cases. Shortly after he received his diagnoses, he lost his ability to walk. This was no doubt a big blow to him as a bright thirteen-year-old who was an avid player of gully cricket: “I was a leg spinner back then,” he recounts. The toughest years, Abhinand said, were when he was in class 11 and 12, when the fact of having to miss out on activities with his friends affected his self-confidence. His school, like almost all others in our country, lacked accessible infrastructure. It was a terrible inconvenience for him to move across floors to attend laboratory sessions and use the washroom.
As he moved on to college, infrastructure and accessibility improved. He was able to participate in activities again and his confidence levels rose. Always fascinated by science, Abhinand was determined to pursue research. While he would have loved to choose genetics or genomics, bioinformatics made most sense for him as most of the work involved computers rather than wet labs. He is today a lecturer at the same university he did his Masters and PhD in.
Abhinand being felicitated at his graduation ceremony
Coming to Sri Ramachandra University, according to Abhinand, felt like he was entering a whole new world. After having visited many other universities in and outside the state, he finds his university one of the most wheelchair-friendly places. Abhinand firmly believes that if governments, organisations and individuals are as accommodating, India would be a better place for people with disabilities. “Everyone should own up to the responsibility and make places more wheelchair-friendly.” At just 33, Abhinand has already authored 14 international peer-reviewed papers and two subject-matter books. He teaches over 200 students every year. Professionally, Abhinand is in a great place.
Last year he joined the Cure SMA Foundation, through which he was finally able to meet and gain the solidarity of many other SMA-affected families in India. This group was formed just in 2014 by parents of children with SMA, but it has grown to have over 700 members now. Abhinand reminds us that this is still only a small fraction of the estimated population of individuals with SMA in India, but that’s not surprising. “Most families are not able to enrol because they are too busy trying to keep their children alive,” he says. Abhinand has always maintained a relatively active social life. “My friends have always compensated for what I lack in genotype… I had the wrong mutation but nature made sure I had the right kinds of friends,” he likes to say. With his friends by his side, Abhinand is occasionally able to indulge his wanderlust. He has travelled quite widely within the country and is eager to do more while he is able to.
Abhinand and his friends at Pangong Lake, Leh
Abhinand is able to manage his lifestyle now with the help of a caregiver. However, as his SMA progresses, things are getting tougher. Without interventions, the quality of his life is likely to deteriorate much further. For the past three decades, there were no options for him, but just a few weeks back, a glimmer of hope shone his way. A drug named Risdiplam was just approved for use in India and this drug can put an end to the progression of his disease.
Thanks to huge advances in biotechnology, bioinformatics and genetic engineering, individuals with SMA now have three life-changing options available to them. The first SMA drug to get approved for the market was Spinraza. It is an injection given 3 to 7 times a year, lifelong. When injected into the fluid surrounding the spinal cord, it enables the back-up smn2 gene to synthesize SMN protein as well as smn1 was supposed to. Sometime in 2019, a more revolutionary gene therapy treatment was approved. Called Zolgensma, it is a one-time injection given to infants with SMA that replaces the defective smn1 gene with a working copy. In this way, it treats the very root of the problem. The third and last treatment option for SMA patients is Risdiplam, which follows a similar strategy as Spinraza to boost SMN levels – it has to be taken orally twice daily for the rest of the patient’s life.
At Rs 18 crore, Zolgensma is currently the most expensive medical drug on the market. Spinraza is not far behind, at Rs 87 lakh per injection – a patient needs 3 to 7 injections every year for the rest of their life. Both need to be imported into India and import taxes and GST adds another few more crores to the cost. Most of the few dozen families that have received these SMA treatments in India did so thanks to pharma company-sponsored ‘compassionate use’ programmes. A handful of others managed to raise the money through crowdfunding and tax waivers from the government.
Having gained approval from India’s DCGI (Drug Controller General of India) just last month, Risdiplam is the only one of these three medications to be available in India. At Rs 6 lakh per bottle (a bottle will last only 12 days and the patient needs it their whole life), it is still expensive enough to be out of reach for almost all Indians. But Risdiplam is Abhinand’s best chance.
“No medication is ever going to make a person like me run or walk again,” says Abhinand, “but Risdiplam can make sure my condition doesn’t get worse. To some extent, there may even be an improvement in my motor movements.” This may not sound like a miracle drug to most of us, but for individuals with SMA this is nothing short of life-saving. It’s the only way for Abhinand to be able to pursue his scientific and personal dreams.
Despite the enormity of the obstacle that lies ahead of him, Abhinand has tremendous faith in humanity. He says that he has never met a ‘really bad’ person throughout his life. Of course, there have been minor irritants which he chalks down to a lack of understanding of disability. “When I go to a restaurant, the waiter or waitress doesn’t talk to me much, instead they ask my friend what I want to eat. Another time, someone told me I am handsome for somebody in a wheelchair… they could instead have said I look good for someone who is 33!” he said, with a chuckle.
If you would like to contribute to Abhinand’s fight for access to Risdiplam, you can contribute to his crowdfunding campaign here: https://www.impactguru.com/fundraiser/donate-to-dr-abhinand-ponneri-adithavarman
(With inputs from Gayatri Padmanabhan)