SINGAPORE - In 2021 , Ms Siti Nur Sabrina Anis, 26, had to swop one set of wheels with another – her Yamaha motorcycle for a motorised wheelchair.

“I used to enjoy riding my motorcycle. It was a great way to de-stress,” said the secretary of charitable organisation Motor Neurone Disease Association Singapore (MNDaSG).

She was in her prime then at 22 when she was diagnosed with amyotrophic lateral sclerosis (ALS).

ALS, also known as Lou Gehrig’s disease, is a rare, terminal neurodegenerative disorder that affects nerve cells in the brain and spinal cord which control voluntary movements and muscle control. The disease causes these nerve cells to atrophy over time and a patient may lose the ability to speak, eat, move and breathe. There is no cure for ALS currently.

It started when Ms Sabrina had problems lifting the front part of each foot. This is known as foot drop and is often due to the compression of a nerve.

“It was at the end of 2021 when I sprained my ankle and I thought my gait was off because of that. However, all the doctors, all the physicians I consulted simply recommended rehabilitation or physiotherapy. They did not really think much about it,” she said.

Soon, it was more than her gait that was affected. The avid sports enthusiast who enjoyed trekking and rock climbing, suddenly could not jump or get up from squats and this unexpected onset of muscle weakness confused her.

Ms Sabrina, who was graduating from the National University of Singapore with a bachelor’s honours degree in Philosophy that year, did not really want to start working “without figuring out what was wrong”.

“I persisted until I found a polyclinic doctor who referred me to the hospital. It took quite a while – a whole semester which was around nine months – to finally get answers ,” she said.

“It was hard to believe that anyone would take nine months to recover from a sprain. I could tell something wasn’t right with my body ... because I was not able to tiptoe or jump , which felt really strange for just a sprained ankle,” she said. 

Ms Siti Nur Sabrina Anis (centre), 26, who has SOD1-related ALS, a terminal condition, with her best friend Luke Ligo (far left), 26, and doctors (from centre) neurologist Dr Kay Ng and geneticist Dr Chin Hui-Lin, both from the National University Hospital.

ST PHOTO: AZMI ATHNI

According to Dr Chin Hui-Lin, a geneticist with the Department of Paediatrics of Khoo Teck Puat - National University Children’s Medical Institute at the National University Hospital, many patients with rare diseases go through what doctors called a diagnostic odyssey.

“It is easier for a physician to diagnose when the symptoms are all florid than when it is gradually progressing. These symptoms can be a bit more insidious early on and look like other conditions, making it difficult for that one physician to tease out that it could be more serious,” she said.

After a battery of tests, which included magnetic resonance imaging (MRI), nerve conduction studies, electromyograms and blood tests, the preliminary findings indicated that Ms Sabrina exhibited signs of neurodegeneration. Nerve conduction studies assess the speed and strength of electrical activity in the nerves while electromyograms measure the electrical activity of muscles and nerves.

In December 2021, she was diagnosed with ALS.

Dr Kay Ng, a neurologist from the Department of Medicine at the National University of Hospital (NUH), told The Straits Times: “ ALS weakness is progressive and intractable, the prognosis is three to five years on average. Usually people who die from the condition die from respiratory failure.”

Typically, ALS is diagnosed more frequently among those who are aged between 40 and 60 years.

“When Sabrina first presented her symptoms, she was 22 – an age which is considered outside the typical age range. This was why the team decided to delve into the possibility of genetic issues ,” Dr Chin said.

Subsequent tests revealed that Ms Sabrina carries a genetic variant in the SOD1 gene, or superoxide dismutase 1 gene. This gene is crucial in protecting cells from the stress caused by an imbalance between free radicals and antioxidants in the body. It also plays a role in other cellular processes like responding to changes in glucose levels.

The prevalence for ALS is about four to seven per 100,000 people globally, but the genetic variant is even rarer, Dr Ng explained.

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“In ALS, you can either be sporadic, which means you have no family history, or it can be familial, where a family history is present . You can find SOD1 mutations in both types, about 2 per cent in the sporadic, and about 20 per cent in the inherited,” she said.

Dr Ng said Ms Sabrina’s case is unique “because we had to combine the usual standard treatment for Lou Gehrig’s disease with the treatment of the knowledge that she has this entity called SOD1-induced ALS”.

“Her treatment involves a whole team of people such as respiratory doctors who monitor her breathing because it is a factor that could contribute to her demise; allied health therapists to help her with physiotherapy; and the palliative team because it is actually a terminal disease. I can imagine how scary that was for Sabrina,” she said.

Ms Sabrina said she did ask “why me ? ”.

“The loneliest (period) was when I was in the hospital... My best friend Luke (Ligo) was m y biggest support. He was then in Perth on an exchange programme then and I thought I had to go through everything on my own until he started calling me every night,” she said.

“I did not really want to tell my parents about my worries because I did not want to freak them out. I did not really want to (put) stress (on) my friends either, so I kept the news to myself.”

Before she could sink in her emotions, the doctors found what they believed was a light at the end of the tunnel.

Biogen, a pharmaceutical company from the United States had come up with a new gene therapy drug called Tofersen targeting the SOD1 gene. Dr Ng and Dr Chin wrote to the drug company “to ask for special permission to be part of their early access programme to bring the drug to Singapore”.

In July 2023, Ms Sabrina got her first dose of Tofersen.

“Sabrina is actually the first person here to receive it. The drug specifically targets the SOD1 m RNA by reducing the accumulation of the abnormal SOD1 protein which causes the nerves to die. It is actually administered to the spinal fluid,” Dr Ng said.

Ms Sabrina goes to the hospital for monthly injections into her spine.

“While some people with SOD1-induced ALS still continue to experience disease progression despite the administration of Tofersen, we have been quite fortunate that the condition has stabilised in Sabrina’s case. We use a scoring system to evaluate her disability levels and were tracking it before we gave the Tofersen. Since then, it has dropped at quite a significant rate,” Dr Ng said.

As for Ms Sabrina, she is taking one day at a time, living her life to the fullest.

From volunteering at MNDaSG in 2023, Ms Sabrina now works full time with the charity, doing what she loves – creating awareness of the condition and counselling those living with it.

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