a gene therapy for spinal muscular atrophy type 1 (SMA1) shows promising
results in its phase 1 clinical trial.
one-time high dose intravenous infusion was shown to extend the survival of
patients with SMA1.
skills like head holding, rolling over, sitting and even walking were observed
in patients who received the therapy.
A recent study published in the New
England Journal of Medicine
reports that a one-time high dose of AVXS-101, a gene therapy for spinal muscular atrophy type 1 (SMA1) extends survival
and helps improve motor function in patients
. SMA is a neuromuscular disease caused by a single
mutation in the SMN gene which results in muscle wasting and lack of motor
skills and control. SMA type 1 (SMA1) is the most severe form and is apparent
at birth. Children with SMA1 have a life span of 2 years and there is no
treatment presently for the devastating disease.
SMA1 is a progressive, childhood, neuromuscular
disease that results in muscle weakness and wastage
. It is caused due to inadequate production of a
protein called survival motor neuron (SMN) encoded by the SMN gene
. The protein is essential for
motor neuron functions. As a result, children with SMA1 fail to meet motor
milestones and usually die by the age of 2 or require permanent mechanical
ventilation in order to survive a litter longer.
1 clinical trial
The study was conducted by research teams at the Nationwide Children's
Hospital and the Ohio State University College of Medicine in collaboration
with AveXis, Inc. AveXis, Inc is a clinical-stage gene therapy company
developing treatments for patients suffering from rare and life-threatening
neurological genetic diseases.
The study was based on administering a one-time intravenous injection of
the SMN gene (AVXS-101) using a modified adeno-associated virus serotype 9 (AAV9)
for delivery. It was tested on 15
‘Gene therapy, AVXS-101, for spinal muscular atrophy type 1 is able to extend the survival of SMA1 patients and improve motor functions in them.’
12 of these patients received a high dose and 3 received a low dose of
AVXS-101. The results suggested that patients who received a high dose showed
improved motor function and required lesser supportive care.
The following were observed in the 12 patients who received the high dose
- 92 percent of patients achieved head control
- 75 percent of patients could roll over
- 92 percent of patients could sit with assistance
- 75 percent of patients are now sitting for 30 seconds or longer
- 2 patients could crawl, pull to stand and stand and walk
As a natural course of disease progression, spinal muscular atrophy
patients require nutritional
and respiratory support by the age of 12 months. They are also incapable of
swallowing or speaking effectively and are almost never able to sit.
Of the patients who received the high dose of AVXS-101,
- 11 patients are able to speak
- 11 patients are fed orally
- 7 do not require bi-level positive airway pressure
as of data assessed until August 7,
the gene therapy
The current gene therapy is the result of almost three decades of
foundational research by teams at Nationwide Children's and Ohio State's Wexner
Medical Center. The SMA mouse model
was a major achievement created by Arthur Burghes, PhD, of Ohio State.
This is the standard model where all therapies including AVXS-101 are initially
tested. Brian Kaspar, PhD, from Nationwide Children's discovered that AAV9 vector was capable of
delivering the SMN gene to the motor neurons in the brain by crossing the blood
brain barrier when injected into the vascular system
. This is the basis of the drug
delivery in the current gene therapy AVXS-101. The phase 1 clinical trials in
humans were possible only after proving that this gene therapy could reverse
the SMN protein deficiency and improve and stabilize SMA in a large animal
This is what Dr. Kaspar, now serving as Chief
Scientific Officer at AveXis had to say about AVXS-101: "At AveXis, we are
enormously pleased to see that all children who received AVXS-101 are alive and
free of permanent ventilatory support at 20 months of age and older - an age
where, sadly, only eight percent of untreated children with SMA Type 1 are
expected to survive without permanent breathing support."
- Jerry R. Mendell et l. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med 2017; 377:1713-1722 November 2, 2017 DOI: 10.1056/NEJMoa1706198
- Spinal Muscular Atrophy (SMA) - (https://my.clevelandclinic.org/health/articles/spinal-muscular-atrophy-sma)