ALS - Potential Therapy

Question 1

What is the current therapy for ALS?

Answer 1

Riluzole

Question 2

What are the acute effects of riluzole?

Answer 2

Decrease in voltage gated Na+ currents
Potentiates Ca2+ dependen K+ current
Inhibits GLU release

Question 3

Where are stem cells used for therapy harvested from?

Answer 3

Bone marrow or umbilical cord blood

Question 4

What must the stem cell be able to do to be an effective treatment

Answer 4

Differentiate, replace and connect with denervated muscle

Question 5

How does stem cell treatment work with mouse embryos?

Answer 5

Treat mice embryo with retinoic acid and sonic hedgehog

With 2 weeks it grows to be a motor neuron

Question 6

Is stem cell treatment a viable option?

Answer 6

In chicks the stem cells migrate to the anterior horn of the spinal cord

Slow the progression and increase survival in rats

But this evidence is limited just now

Question 7

Why might ceftriaxone help ALS?

Answer 7

Increases glial cell mediated glutamate transport (via stimulation and upregulation of EAAT2 mRNA)

Question 8

What is the main aim of muscle therapy?

Answer 8

To improve diaphragm function

Question 9

How does ACE-031 work?

Answer 9

Inhibits negative regulators of muscle growth

(like myostatin)

(ie promotes muscle growth)

Question 10

How is ACE-031 given?

Answer 10

Subcut

Good tolerance

Question 11

How does CK-2017357 work?

Answer 11

Activates fast skeletal muscle troponin by increasing muscle sensitivity to Ca2+

Question 12

What is the overall effect of CK-2017357?

Answer 12

Increase muscle force to improve pulmonary function

Question 13

Which proteins are involved in protein folding and degradation?

Answer 13

Heat shock proteins

Question 14

What does arimoclol do?

Answer 14

Penetrates the CSF to increase the expression of neuroprotective HSPs
This delays disease progression and increases lifespan

Question 15

How is arimoclol given?

Answer 15

Orally

Question 16

Explain why using RNA could help treat ALS

Answer 16

anti-sense oligonucleotides and small inhibitory RNAs

To bind to mutant RNA and stop if form being translated

This slows disease progression and increases survival in transgenic mice

Question 17

What is the main issue for RNA targeted therapies?

Answer 17

Only work on known mutations

Question 18

What does ISIS333611 do?

Answer 18

Intrathecally targets mSOD1 to reduce its gain of function

Question 19

What is olesoxime?

Answer 19

Mitochondrial pore modulator which delays onset and extends survival

Question 20

Does creatinine affect ALS symptoms?

Answer 20

Seems to in transgenic mice

Question 21

What does dexpramipexole do?

Answer 21

Decreases the oxidative stress
Maintains mitochondrial function
Extends survival
Well tolerated

Question 22

What is HUR?

Answer 22

An mRNA stabiliser which binds to VEGF RNA to enhance protein production

Question 23

How is HUR affected in ALS?

Answer 23

binds competitively to mSOD1 instead of VEGF RNA

So there is less VEGF so less neuroprotection

Question 24

What has intracerebroventricular VEGF been shown to do?

Answer 24

Increase MN survival and increase O2 supply

Question 25

Which recent evidence suggests stem cells could treat ALS?

Answer 25

Adipose-derived stem cells can accurately reach targets and form connections in both upper and lower motor neurons

At intermediate stage ALS

Walker 2019

Question 26

How does olesoxime work?

Answer 26

Modulates mSOD1 and Ca2+ entry to the mitochondria