I work adjacent to this field (gene therapy), so while I do not have direct experience with MLD (the disease) nor the development of Libmeldy (the drug), I am able to peruse the data pretty well.
First, it seems clear that the cause is MLD is well-known: the deficiency of the enzyme arylsulfatase A (ARSA), which results in activity in leukocytes less than 10% of normal function. With this level of function, sulfatides build up in various tissues, eventually resulting in the destruction of the myelin sheath that is essential for nerve function. MLD is autosomal recessive, with ARSA located on chromosome 22.
So, a direct answer to your question is that since leukocytes are the cell types where the deficiency of this enzyme results in the disease state, the gene therapy which results in a new, functional version of ARSA in the stem cells which will differentiate into said leukocytes will restore efficiency of this enzyme to levels that alleviate the disease state. It would appear that restoring functionality in this specific cell type (CD34+ stem cells) is sufficient.
Some interesting notes:
The girl treated was very young, which seems to be crucial in rescuing function. Her older sister also has MLD, but her disease had progressed too far to be a candidate for the drug. Super sad and super unlucky: the parents had only a 1-in-16 chance that both of their children would have the disorder, as the parents were both carriers.
Obviously, long-term effects of this treatment are not known, as it has only recently been approved. But, researchers expect that the treatment should be lifelong because the lentivirus vector integrates into the CD34+ cells and should persist as long as that population of cells remains in the bone marrow.
The price for this drug (and other life-long gene therapy treatments) is incredibly high (in this case, I've seen 2.8 million pounds sterling quoted). This poses a number of challenges from a reimbursement standpoint, and frankly the field does not know what the best way forward is going to be. The interaction between companies, regulators, insurance, patients, etc. are all quite nuanced and the specifics differ between each of these therapies. Putting aside any ethical considerations for drugs priced this high, the actual financial logistics will always be an issue.
TrenchantPergola t1_j8nhyq5 wrote
Reply to Recently a gene therapy for a rare inherited neurodegenerative disorder was approved. How come cure is achieved through bone marrow transplantation? by nickoskal024
I work adjacent to this field (gene therapy), so while I do not have direct experience with MLD (the disease) nor the development of Libmeldy (the drug), I am able to peruse the data pretty well.
First, it seems clear that the cause is MLD is well-known: the deficiency of the enzyme arylsulfatase A (ARSA), which results in activity in leukocytes less than 10% of normal function. With this level of function, sulfatides build up in various tissues, eventually resulting in the destruction of the myelin sheath that is essential for nerve function. MLD is autosomal recessive, with ARSA located on chromosome 22.
So, a direct answer to your question is that since leukocytes are the cell types where the deficiency of this enzyme results in the disease state, the gene therapy which results in a new, functional version of ARSA in the stem cells which will differentiate into said leukocytes will restore efficiency of this enzyme to levels that alleviate the disease state. It would appear that restoring functionality in this specific cell type (CD34+ stem cells) is sufficient.
Some interesting notes:
The girl treated was very young, which seems to be crucial in rescuing function. Her older sister also has MLD, but her disease had progressed too far to be a candidate for the drug. Super sad and super unlucky: the parents had only a 1-in-16 chance that both of their children would have the disorder, as the parents were both carriers.
Obviously, long-term effects of this treatment are not known, as it has only recently been approved. But, researchers expect that the treatment should be lifelong because the lentivirus vector integrates into the CD34+ cells and should persist as long as that population of cells remains in the bone marrow.
The price for this drug (and other life-long gene therapy treatments) is incredibly high (in this case, I've seen 2.8 million pounds sterling quoted). This poses a number of challenges from a reimbursement standpoint, and frankly the field does not know what the best way forward is going to be. The interaction between companies, regulators, insurance, patients, etc. are all quite nuanced and the specifics differ between each of these therapies. Putting aside any ethical considerations for drugs priced this high, the actual financial logistics will always be an issue.
Hope that helped. Cheers!