Looking towards gene therapy to give baby Ginny a normal life

SINGAPORE – A teacher at baby Ginny’s infant-care centre was the first to observe that, unlike other babies her age, Ginny was not holding her head up during tummy time. At that point, she was three months old.

Around the same time, Ginny’s parents took her for a routine developmental check-up.

“Our paediatrician, who is also a paediatric neurologist, noticed some developmental delays and said this could be a normal occurrence and advised monitoring,” her mother, Ms Jenny Mak, 31, said.

But her parents continued to be concerned as Ginny was persistently not lifting or turning her head, or rolling over onto her tummy – the typical milestones of early infancy.

“She was alert and responsive like any baby her age. But her body wasn’t moving the same way. Her legs barely moved,” Ms Mak said.

Wanting a second opinion, Ms Mak took her daughter to another child specialist and was again reassured that developmental timelines vary among children.

It was in late January that 14-week-old Ginny developed fever and flu-like symptoms and was given medication prescribed by her paediatrician, including nebulisation, but later that night, her condition deteriorated.

“Her lips turned purple, her cry became weak, and she appeared less responsive. We called for an ambulance and took her to hospital where she was admitted.

“But her condition worsened over the next few days... She was diagnosed with pneumonia and was transferred to the ICU (intensive care unit) for respiratory support,” Ms Mak told The Straits Times.

“It was extremely difficult to watch her, and our immediate focus was on her recovery. We relied on the medical team, hoping for the best outcome,” she added.

Ginny continued to struggle to breathe after being discharged from hospital and watching her do so was “heartbreaking”.

Her parents decided to return to KK Women’s and Children’s Hospital (KKH) for further investigation.

“She was struggling to clear the phlegm from her lungs, leaving her chest heavily congested. Even drinking milk became difficult because she couldn’t cough effectively,” her mother said.

Ginny underwent genetic testing in late February and was diagnosed with spinal muscular atrophy (SMA) Type 1, a genetic condition that affects motor nerve cells in the spinal cord, causing progressive muscle weakness.

If left untreated, it leads to profound muscle weakness, paralysis and severe respiratory compromise, with the baby eventually dying before age two.

According to Ginny’s doctor, Dr Jocelyn Lim, a senior consultant with the neurology service at the Department of Paediatrics at KKH, Type 1 SMA is the most common and severe type of SMA, with symptoms showing up within the first six months of life.

“Type 1 SMA patients like Ginny will have low muscle tone, poor neck control and poor leg movements. They also have difficulties swallowing and feeding, and often have poor weight gain. They can have frequent respiratory infections that take longer to recover from,” Dr Lim told ST.

Tongue fasciculations or quivering and a lack of reflexes are also characteristics of the disorder, she added.

Dr Lim said the condition is caused by two defective copies of a gene inherited from both parents, and not caused by environmental factors, such as the mother’s diet or infections acquired during pregnancy.

Globally, about one in 10,000 people has Type 1 SMA, and in Singapore, there is an average of one to two patients a year.

Treating, managing Type 1 spinal muscular atrophy

“As motor neurones are irreversibly lost, patients get progressively weaker, resulting in respiratory damage, feeding difficulties and failure to thrive. They will require long-term respiratory and feeding support, without which most Type 1 patients do not survive past two years and may succumb, most commonly to respiratory infections,” Dr Lim added.

She said general practitioners and paediatricians “need to have a high clinical suspicion of SMA to direct patients urgently to tertiary hospitals for diagnosis”.

“The earlier the diagnosis and treatment, the better the outcomes. (If the treatment is) initiated before symptoms appear, it can even result in reaching normal motor milestones,” Dr Lim explained.

Having a rare disease, which is defined as one that affects fewer than one out of 2,000 people, can often feel like being handed the short end of the stick.

Due to their rarity and non-specific symptoms, many conditions can slip through the cracks or go unnoticed.

There are about 3,000 people in Singapore living with rare conditions, and while some were diagnosed in infancy, others were diagnosed in childhood or even adulthood. To date, 7,600 genetic conditions have been identified, and more are being discovered every year.

However, genetic testing often may not be done early for a patient with a rare condition, as most doctors tend to test for common treatable conditions first, among other factors. Consequently, it may take between three and 15 years before a rare disease is accurately diagnosed.

“For Type 1 SMA in Ginny, it can be either gene therapy like Zolgensma, which replaces the missing SMN1 (survival motor neuron 1) gene, or oral medication such as Risdiplam, and spinal injections. These therapies must be accompanied by multi-disciplinary care, which includes regular physiotherapy, occupational therapy, nutritional, respiratory and orthopaedic management,” Dr Lim said.

She added that for all therapy types, how early treatment starts is the greatest determinant of outcome.

Dr Lim said disease-modifying therapies for rare genetic conditions are often costly worldwide because they involve complex research and development.

She said the hospital works closely with its medical social workers to help families navigate all available financial assistance schemes and support them “through this challenging journey”.

In Singapore, Risdiplam costs about $5,000 a bottle, and dosage is dependent on the patient’s weight. Eligible patients in public hospitals may receive up to 75 per cent subsidies for it.

Dr Lim said the maximum dosage is five bottles every two months when the patient reaches 20kg and above.

However, there is currently no spinal injection therapy available in Singapore.

“Risdiplam is now subsidised and included under MediShield Life, which has been a significant game changer in making this lifelong treatment more accessible for families who qualify for assistance,” she said.

“Gene therapy Zolgensma can give a full recovery when it is started before but not after symptoms show, because motor neurones are already irreversibly lost,” Dr Lim said.

“However, Zolgensma is a one-time treatment but is currently not subsidised. This is why some families explore alternative avenues, such as crowdfunding to support the cost of treatment,” she added.

Ms Mak said that as parents, their priority was to give Ginny the best possible chance of survival.

“While the cost of treatment is significant and beyond what we can afford on our own, we focused on exploring all available options. With the support of a medical social worker, we applied for the Ministry of Health MediFund. Unfortunately, we learnt that Zolgensma is not included under the ministry’s cell, tissue and gene therapy product list, which insurers refer to,” she said.

Given the time-sensitive nature of the condition, Ms Mak and her husband turned to crowdfunding charity Ray of Hope to raise funds for the gene therapy.

“We learnt that other families in similar situations had successfully raised funds there, and we launched our campaign on March 12 to mobilise community support for our daughter,” she said.

As at March 20, the charity has raised 79 per cent of the total cost of the gene therapy, which is about $2.4 million.