Have you ever finished a painfully long math problem, only to realize you made a mistake in the very first step? Although you probably panicked because your final answer was embarrassingly far away from the correct one, fixing your one small mistake may have actually revealed that the mess was not truly all that complicated. Identifying the root of a seemingly drastic problem quite frequently uncovers the underlying simplicity of the matter, but who would have thought that this basic concept could save generations of victims of a viciously lethal disease?
Mucolipidosis type II is an extremely rare inherited disease that causes physical, mental, and visual deformities and usually claims its victims before they turn seven years old (oftentimes much sooner). What causes Mucolipidosis type II? Simply put, it is when lysosomes do not receive the enzymes necessary to digest materials, making them not only ineffective, but also dangerous. When lysosomes are unable to perform the necessary recycling functions that you have learned about in AP Biology, materials are instead stored in the cell, causing Mucolipidosis type II and its seemingly infinite list of tragic symptoms such as scoliosis, neurological disabilities, ectrodactyly, enlargement of the heart, and more.
In fully functional cells, mannose-6-phosphate biosynthetic pathway, or M6P, signals the transport of hydrolytic enzymes into the lysosomes. Inversely, when M6P is either not functional or not present, the hydrolytic enzymes do not make it to the lysosomes, causing Mucolipidosis type II. Now that we know what happens when M6P is dysfunctional, let’s take one more step back. What causes M6P to stop working in the first place? Well, it turns out that a team of scientists at the University of Michigan had the same question.
Using CRISPR technology, the team tested individual genes’ effects on cellular functions, and they found the answer to our previous question: TMEM251. This gene is responsible for creating an enzyme called GNPT, which signals M6P to transport the enzymes to the lysosomes, and when this one singular gene fails to work, it causes the lifelong adversities of Mucolipidosis type II. Also, TMEM251 is located in the Golgi apparatus, and you (hopefully) already learned in AP Biology that lysosomes are created from this organelle. Therefore, this fact further supports the validity of the new finding.
The disease currently has a 100% fatality rate because scientists have not yet discovered a cure. Or have they? Now that scientists have identified the root of the problem, non-functional TMEM251 genes, they are experimenting with enzyme replacement therapy- the supplementing of missing lysosomal enzymes into the cell through endocytosis– to rehabilitate the cells to their proper, functional forms. It may be too early to place bets, but this groundbreaking discovery could turn out to be the hope that scientists around the globe have been searching for.