The Future for Neurodegenerative Diseases: Regenerative technology
Envisioning a future where damaged nerves could be regenerated with just a pill.
This could be possible with the integration of regenerative medicine and technology.
How do nerves function?
Consider this. A spider crawls on your forearm so you startle and slap it off. You touch a hot plate and reflexively pull back your hands as your nerves simultaneously deliver pain signals to your brain.
How can one kind of cell carry out so many functions?
Billions of nerve cells, also known as neurons, are found in the nervous system. Each of these neurons is highly specialized to carry nerve impulses. Neurons can only be detected using a microscope and can be split into three sections:
- Soma (cell body): receives information and contains the cell’s nucleus
- Dendrites (“input” part of the cell): thin filaments that carry information from other neurons to the soma.
- Axon (“output” part of the cell): long projection carries information from the soma and directs it off to other cells.
The signals that neurons receive accumulate until they exceed a particular threshold. Once the threshold is exceeded, the neuron is triggered to deliver an impulse (referred to as an action potential) along its axon. An action potential is generated by the movement of ions across the axon’s membrane. At rest, neurons are more negatively charged than the fluids that surround them.
Nerves are fragile and can be damaged by stretching, cutting, or pressure. The damage may occur when an axon gets inflamed or when the myelin (an insulating layer that forms around nerves) is stripped away from the axon– causing information that passes along a demyelinated nerve to become blocked or delayed. This means that you can potentially damage your nerves simply from a slip and fall. There are more than 100 different types of nerve damage. Around 20 million Americans suffer from peripheral (related to the five senses) nerve damage– which has become increasingly common with age. Nerve injuries may result in serious consequences like neurodegenerative diseases and paralysis.
Our solution: Introducing “BetaMax Nano Pills”
A nanobot is essentially a term for molecules with a unique property that allows them to be programmed to implement a specific task. Nanobots are able to move autonomously, making it possible to deliver drugs to ‘hard-to-reach’ areas while reducing the chances of possible side effects. They are driven by exogenous power such as light energy, electric fields, magnetic fields, acoustic fields, etc. Multiple benefits can be derived from nanoparticles due to their small size, chemical stability, and surface functionalization.
We hope to leverage two sets of nanobots for the purpose of:
- Monitoring and tapering the dependency of serotonin in particular areas.
- Delivering and releasing serotonin to a precise location.
Monitoring and tapering the dependency of serotonin in the particular areas
By monitoring the dependency of serotonin in particular areas, an estimated amount of serotonin that is needed to initiate the regeneration process can be made. The amount of serotonin released will be precisely controlled so that there is enough serotonin to attract neurons nearby and not an excessive amount of serotonin that nerve cells become overly dependent on.
Delivering and releasing serotonin to a precise location
A study was conducted where nanobots were used to monitor the blood sugar level. Special sensor nanobots were positioned under the skin into the blood where microchips coated with molecules were intended to emit electrical impulse signals and monitor blood sugar levels. When drug carrier nanobots detect hints of the disease, wires would emit electrical pulses that would dissolve the walls of the drug to be released. This allowed users to easily control the amount and time of the drug release by simply controlling the electrical pulse.
Rather than detecting signs of diseases, we want to detect areas with damaged nerves.
How is serotonin used to regenerate nerves?
A previous experiment performed on a tadpole can explain the nature of nerve regeneration using serotonin. Cyclic adenosine monophosphate (cAMP) is a second messenger, consisting of small molecules and ions, that transmit signals from receptors to effector proteins. In this study, it was shown to promote axon regeneration following spinal cord injury(SCI).
There were different families of serotonin receptors (5-HT); families 1 and 5 of 5-HT receptors lowered cAMP levels whereas families 4, 6 and 7 increased cAMP levels. The 5-HT helped in the modulation of axon regrowth and in the generation of new neurons in the nervous system of regenerating species.
After a tadpole’s fin was soaked in serotonin, the charge of the cells in the fin region was made more positive as serotonin is naturally positively charged. Since neurons have a fairly negative charge when at rest, they will be attracted to the area of the serotonin.
Why do neurons have a negative charge at rest?
The resting potential (when neurons are at rest) is negative due to the accumulation of more sodium ions (Na+) outside the cell than potassium ions (K+) inside the cell. Potassium ions diffuse out of the cell at a faster rate than the rate at which sodium ions diffuse into the cell because there are more potassium leak channels than sodium leak channels. Sodium-potassium pumps transport three sodium ions out of the cell and two potassium ions into the cell every cycle.
leak channels: channels that allow ions to pass through membranes without any impedance. Ions move down its concentration gradient (from higher concentration to lower concentration).
*pumps: use a source of free energy like ATP or light to transport ions against the concentration gradient (from lower concentration to higher concentration).
Adding the 5-HT receptors which increased cAMP levels, allowed the fin to regenerate axons in the spinal cord. In this study, approximately 50% of descending brainstem neurons were able to regenerate their axons under the site of injury after a complete spinal cord injury.
They confirmed this observation with an alternative experiment conducted at Tufts University, where an eye tissue was attached to the tadpole's flank. They soaked the tissue in Zolmitriptan, a “selective serotonin receptor agonist” commonly used in migraine medication. An agonist is a molecule capable of binding and activating receptors in the brain which then started a biological response.
The biological response, in this case, was the stimulation and activation of the eye tissue to detect light. It was then observed that an optic nerve has found its way down the spinal cord to the eye tissue and hence, sensed light. Using this ability, our targeted serotonin medication will be able to regenerate nerves when they are damaged.
The outcomes of this particular study revealed that Zolmitriptan has a strong effect on the growth and connection of nerves between host nervous systems and grafted organs– proposing a new future for regenerative medicine.
Future Research
There are still a few elements that must be explored before the solution can be fully implemented.
Firstly, most of the previous studies were performed on invertebrates. Thus, more research must be done to discover a method to apply these same studies to humans. In the past, the recovery process from spinal cord injuries from lampreys was indicated.
The recovery process implies…
- A positive response of astrocytes.
- Producing new neurons in the spinal cord area.
- Regenerating ascending and descending axons through injured locations.
The Department of Functional Biology at the University of Santiago de Compostela stated, “The current challenges facing nerve regeneration is to locate signals controlling cAMP levels in descending neurons after axotomy and during regeneration.” In order to discover the application of nerve regeneration in humans, biomimicry can be utilized to mimic the regeneration process of lampreys.
In addition, the appropriate amount of serotonin required for nerves to regenerate must be researched further. An excess or lack of serotonin may affect the injury sites’ original dependency on serotonin.
TLDR
- Peripheral nerves are very important and fragile.
- Using nanobots, we can deliver and release the appropriate amount of serotonin to specific parts of the body with damaged neurons.
- The serotonin is able to attract neurons from other areas and causes nerve endings to regenerate.
- One study demonstrated the nature of nerve regeneration in the fin of a tadpole.
- A second study supported the first study by revealing how they restored the sight of a tadpole when an optic nerve descended down the spinal cord to the eye tissue.
- Biomimicry can be leveraged in the future to apply the previous studies (which were conducted on invertebrates) on humans.
To learn more about BetaMax, check out this website: https://www.betamax.tech/
Collaborated with Varsha Prasad and Nicholas Singh.
