Rock climbing fan suddenly could not jump, get up from squats

SINGAPORE – In 2021, Ms Siti Nur Sabrina Anis, 26, had to swop one set of wheels for 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 the Motor Neurone Disease Association Singapore (MNDaSG), a charitable organisation.

She was 22 when she was diagnosed with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.

ALS is a rare, terminal neurodegenerative disorder that affects nerve cells in the brain and spinal cord, which control voluntary movements and muscle function.

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 currently no cure for ALS.

It all began when Ms Sabrina had trouble lifting the front part of each foot. This is known as foot drop, which 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, more than just her gait was affected. The avid sports enthusiast, who enjoyed trekking and rock climbing, suddenly could not jump or get up from squats.

This unexpected onset of muscle weakness confused her.

At that time, Ms Sabrina was graduating from the National University of Singapore with an honours degree in philosophy. She did not want to start working “without figuring out what was wrong”.

“I persisted until I found a polyclinic doctor who referred me to a hospital. It took quite a while – 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.”

According to Dr Chin Hui-Lin, a geneticist with the department of paediatrics at Khoo Teck Puat – National University Children’s Medical Institute at the National University Hospital (NUH), many patients with rare diseases go through what doctors call a diagnostic odyssey.

“It is easier for a physician to diagnose when the symptoms are all florid (or in the fully developed form) 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, 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 November 2022, Ms Sabrina was diagnosed with ALS.

Dr Kay Ng, a neurologist from the department of medicine at 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 in people aged between 40 and 60.

Dr Chin said: “When Sabrina first presented her symptoms, she was 22 – an age that is considered outside the typical age range.

“This was why the team decided to delve into the possibility of genetic issues.”

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, such as responding to changes in glucose levels.

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

“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 added that 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 asked herself, “Why me?”

“The loneliest (period) was when I was in the hospital... My best friend Luke (Ligo) was my biggest support. He was 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 into her emotions, the doctors found what they believed was a light at the end of the tunnel.

Biogen, a pharmaceutical company from the US, had come up with a new gene therapy drug called Tofersen targeting the SOD1 gene. Dr Ng 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.

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

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

Dr Ng said: “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.”

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

In 2023, she began volunteering with MNDaSG, doing what she loves – creating awareness of the condition and counselling those living with it.