What Researchers are Doing to Cure Krabbe Disease
What is Krabbe Disease?
Krabbe disease is a severe neurological disorder that affects 1 in every 100,0000 people. It affects the development and function of the nervous system. It is inherited in an autosomal recessive manner, meaning both parents must be carriers of a mutated gene in order for their child to develop it. Symptoms of Krabbe disease become apparent before the age of 1, and since the condition is so severe, individuals with Krabbe disease rarely survive past the age of 2.
Krabbe disease begins innocuously and can be difficult to diagnose if not screened for after birth. It may first start with muscle weakness, difficulty feeding, inexplicable fevers, and irritability. As the disease progresses, mental and physical development becomes delayed, the patient’s ability to eat and speak decreases, vision loss occurs, and seizures become frequent.
What is Krabbe Disease Caused by?
Krabbe disease is caused by a mutation in the GALC gene. The GALC gene is responsible for making the enzyme called galactosylceramidase. Galactosylceramidase works alongside water molecules through hydrolysis in order to break down galactolipids (fats) found in the nervous system. A specific galactolipid called psychosine is toxic to cells and because it doesn’t get broken down due to the mutation in the GALC gene, psychosine accumulates in toxic levels and causes the loss of myelin in the nervous system. Myelin is a protective layer that envelops nerve cells and ensures that neurons can communicate between one another rapidly. However, since myelin is lost, neurons deteriorate and die.
What Treatments Are There?
Bone marrow transplants, otherwise known as hematopoietic stem cell transplants, have so far been the most promising treatment to extend the lives of those with Krabbe disease. Patients must receive the transplant as early as possible, however, since individuals in which Krabbe disease has progressed significantly have been found to have complications with the transplant. Bone marrow transplants work by removing stem cells which have abnormal levels of enzymes and replacing them with cells which have normal levels of enzymes. By having healthy blood-forming cells, the patient can break down galactolipids and psychosine. The transplant cannot revert damage that has already been done, but will ensure no further damage is done to the neurons. Unfortunately, the transplant doesn’t effectively correct the mutated GALC gene, so as patients develop, they will progressively lose motor function, which will result in death.
What New Research is There for Krabbe Disease?
Gene therapy is often a potential solution to treat rare diseases like Krabbe disease, since it can address the underlying cause of the disease, and not just the symptoms of it, holding promise to be a definite cure. Forge Biologics has received FDA Fast Track status for their gene therapy called the FBX-101. The FDA gives Fast Track status when a drug is determined to address an urgent unmet clinical need for life-threatening conditions.
FBX-101 is an AAV (adeno-associated viral) gene therapy that typically follows a bone marrow transplant. The virus has been genetically engineered to ensure it produces no immune reaction. It instead functions as an empty vehicle that delivers a healthy or functional copy of the GALC gene to neurons, which would then be able to produce the enzyme required to break down psychodine. Therefore, toxic levels of psychodine would no longer accumulate in the brain. In mouse models, FBX-101 corrected deficiencies in myelin, improved behavior impairments, and significantly extended the life spans of treated animal models. There is currently a Phase 1/2 clinical trial, seeking to determine the safety and efficacy of the FBX-101 in patients with Krabbe disease.
Thank you so much for taking the time to read this article! I write in order to raise awareness for rare diseases and the exciting research taking place to pave a way to a cure! If you enjoyed this read, you can check out some of my previous articles linked below.
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