It’s a complex, progressive and deadly disease. ALS patients deteriorate quickly – their bodies breakdown, but not their minds. Now the brain power of a local research team has shed light on a critical component of the disease. The breakthrough may finally bring patients a glimmer of light.
Connie Becker’s connection to ALS is overwhelming – 18 family members have fought the incurable disease. The latest – two cousins who know, like the others, they will soon die.
“Watching them struggle to even sit up, take a breath, give a hug. It’s heartbreaking to watch. And ultimately they are not able to do anything. Their mind stays the whole time, which is even more heartbreaking because you know they know what’s happening. We have been wanting and needing something so desperately. There have been so few breakthroughs,” she said.
ALS researcher at Northwestern Medicine, Hande Ozdinler hopes her team’s recent breakthrough will change the course of Connie’s family history.
“Much of the focus has been on the spinal cord, and the cortex has been mostly ignored because the cortical motor neurons are not easy to identify, are not easy to label and they are very few in numbers,” Ozdinler said.
But they are critical in understanding ALS. As motor neurons in the spinal cord and brain’s cortex break down, so does the body.
“For each movement that you make that you think about, you use your cortex — to grasp an object, turn a key, dial a phone — your cortex is involved. In ALS, these neurons die and we need to find out why they are vulnerable and why they degenerate together with the spinal neurons,” Ozdinler said.
The first challenge — she had to find a common denominator among the motor neurons, which blend in a pool of 2 billion neurons in the central nervous system. She searched through 6,000 genes until she found one expressed in both spinal cord and cortex motor neurons. Then she delivered a dose of green fluorescence to highlight her target.
It’s intact and full bodied, able to deliver messages from the brain to the body, a stark contrast to a diseased neuron.
“They are shredded apart. They are very sick looking and their cell bodies, they shrink. This is a very sick upper motor neuron. If we can find out what goes wrong in these neurons, then it will be easy for us to build an effective cellular therapy. Then we will go to patients and say, ‘Ok, this is what you need,’” Ozdinler said.
And that’s the next step — to test different drugs and therapies that may stop the neurons from deteriorating.
The research was supported by the Les Turner ALS Foundation, the Wenske Foundation and the Brain Research Foundation and grants NS050162, P30 NS054850–01A1, NS061963 and F32 NS063535 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health and NIH MAD Training Grants 5T32AG020506–09 and 5T32AG020506–10.
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