Latest / Glaucoma, Vision & Longevity: Supplements & Science / Nerve Growth Factor–Based Peptides and Optic Nerve Protection

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Nerve Growth Factor–Based Peptides and Optic Nerve Protection · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: Introduction.
• 0:01
  SPEAKER_00: Glaucoma is a common cause of vision loss that happens when the retinal ganglion cells, RGCs, the nerve cells connecting the eye to the brain, gradually die.
• 0:11
  SPEAKER_00: As one review notes, glaucoma is characterized by RGC degeneration and loss of visual field.
• 0:17
  SPEAKER_00: In other words, patients slowly lose side vision and eventually central vision.
• 0:22
  SPEAKER_00: Current glaucoma medicines all lower eye pressure, but doctors are actively looking for ways to protect the optic nerve cells directly.
• 0:29
  SPEAKER_00: One idea is to use nerve growth factor, NGF, a natural protein that helps nerves survive and grow.
• 0:35
  SPEAKER_00: NGF is like a fertilizer for certain nerve cells.
• 0:38
  SPEAKER_00: In healthy eyes, it supports RGC survival.
• 0:40
  SPEAKER_00: In glaucoma, NGF levels may drop, so adding extra NGF might slow RGC loss.
• 0:46
  SPEAKER_00: NGF and neuroprotection.
• 0:48
  SPEAKER_00: NGF is a small protein, a neurotrophin, that binds to receptors on neurons and tells them grow and live.
• 0:55
  SPEAKER_00: Animal and lab studies show NGF plays a crucial role in neuronal survival, differentiation, and growth.
• 1:01
  SPEAKER_00: In the eye, retinal ganglion cells have NGF receptors, meaning they can respond when NGF is present.
• 1:07
  SPEAKER_00: The idea is that supplying more NGF could neuroprotect these cells.
• 1:11
  SPEAKER_00: In other words, NGF might block the cell death signals in glaucoma and keep RGCs alive longer.
• 1:18
  SPEAKER_00: It's important to note that NGF medicines already exist for other eye conditions.
• 1:22
  SPEAKER_00: In 2018, the FDA approved a topical NGF eye drop, trade name oxurvate, generic senogermin, to treat neurotrophic keratitis, a corneal surface disease where the cornea heals badly.
• 1:35
  SPEAKER_00: This eyedrop is not approved for glaucoma.
• 1:38
  SPEAKER_00: Using it for glaucoma would be off-label, meaning doctors could legally try it, but insurers usually won't pay, and scientists don't yet know if it works for that use.
• 1:47
  SPEAKER_00: So far, any NGF treatment of glaucoma patients is experimental and done outside official guidelines.
• 1:54
  SPEAKER_00: NGF in Animal Glaucoma Studies.
• 1:56
  SPEAKER_00: Several animal experiments suggest added NGF can protect the optic nerve.
• 2:01
  SPEAKER_00: In one rat study, glaucoma induced by high pressure, the untreated eyes lost about 40% of their RGCs in seven weeks.
• 2:09
  SPEAKER_00: The rats given NGF eye drops lost much fewer nerve cells.
• 2:13
  SPEAKER_00: In fact, researchers reported that NGF treatments significantly inhibited the programmed death of RGCs.
• 2:19
  SPEAKER_00: Another rat study found similar results.
• 2:22
  SPEAKER_00: High eye pressure caused serious retinal damage, but daily NGF eye drops significantly reduced the deficit of RGCs compared to untreated eyes.
• 2:30
  SPEAKER_00: In short, in multiple rodent models, topical NGF slowed nerve cell loss deepened the retina.
• 2:36
  SPEAKER_00: In a rabbit glaucoma model, pressure raised by a gel in the eye, researchers injected NGF around the eye, retrobulber, before damage.
• 2:44
  SPEAKER_00: Those rabbits also had less optic nerve damage, while blocking NGF at the same time made damage worse.
• 2:50
  SPEAKER_00: Taken together, these animal results support the idea that NGF can rescue RGCs from glaucoma-like injury.
• 2:57
  SPEAKER_00: NGF and Clinical Studies, Small Human Reports.
• 3:01
  SPEAKER_00: Clinical evidence in humans is still very limited.
• 3:04
  SPEAKER_00: In one open label report, three patients with severe, progressive glaucoma were given NGF eye drops along with their normal pressure medicines for three months.
• 3:14
  SPEAKER_00: These were patients whose vision was worsening despite good pressure control.
• 3:19
  SPEAKER_00: After treatment, all three showed long-lasting improvements in various vision tests.
• 3:24
  SPEAKER_00: Specifically, their visual field test results improved, their optic nerve electrical signals, pattern ER, got better, and even contrast sensitivity and visual acuity improved.
• 3:36
  SPEAKER_00: This is compelling but very preliminary.
• 3:39
  SPEAKER_00: There was no control group, and such a small series can't prove effectiveness.
• 3:43
  SPEAKER_00: No large clinical trials of NGF and glaucoma have been done yet.
• 3:47
  SPEAKER_00: Most NGF clinical work has focused on cornea and retina diseases.
• 3:51
  SPEAKER_00: But these case reports suggest NGF eye drops might help vision and glaucoma.
• 3:56
  SPEAKER_00: Doctors would measure success in a real trial by things like the OCT nerve fiber layer thickness to see if nerve tissues are preserved and standard visual field tests to see if vision loss slows.
• 4:08
  SPEAKER_00: In the small study, improvements were seen in visual field scores and electrical measures, which hints at real functional benefit.
• 4:16
  SPEAKER_00: NGF-derived peptides and future therapies.
• 4:20
  SPEAKER_00: Because NGF is a large protein that can be hard to deliver, researchers are also exploring NGF mimicking peptides.
• 4:28
  SPEAKER_00: These are short chains of amino acids designed to act like NGF by activating the same receptor, TARCA, on neurons.
• 4:35
  SPEAKER_00: For example, one group designed small peptides corresponding to two loops of the NGF molecule.
• 4:40
  SPEAKER_00: These peptides bound TARCA and triggered the same growth signals as NGF.
• 4:45
  SPEAKER_00: In nerve injury experiments in rats, the most effective peptide called L1L4 reduced nerve damage and pain, much like NGF did.
• 4:53
  SPEAKER_00: While this work was on peripheral nerves, not the eye, it shows proof of concept.
• 4:58
  SPEAKER_00: NGF-like peptides can protect neurons.
• 5:01
  SPEAKER_00: In the future, similar peptides might be tested for the optic nerve.
• 5:04
  SPEAKER_00: Such peptide drugs could be cheaper and more stable than full NGF, but they are still in early lab stages.
• 5:11
  SPEAKER_00: Dosing and delivery, drops versus injections, the approved NGF drugermin is given as eye drops, one drop in the affected eye six times a day for eight weeks.
• 5:22
  SPEAKER_00: This regimen was tested in corneal disease trials, and it appears NGF can reach the back of the eye that way.
• 5:28
  SPEAKER_00: In the glaucoma studies above, researchers generally use topical drops as well.
• 5:33
  SPEAKER_00: In contrast, direct injections of NGF into or near the eyeball are not used in people, because systemic NGF causes severe pain and injecting into the eye risks complications.
• 5:45
  SPEAKER_00: However, animals sometimes receive local injections.
• 5:48
  SPEAKER_00: Rabbits got a needle behind the eye, retrobulber, with NGF before glaucoma injury, and this helped protect their nerves.
• 5:56
  SPEAKER_00: It's thought that injections could deliver more NGF into the optic nerve region.
• 6:01
  SPEAKER_00: But for now, the safer tested form is the eye drop.
• 6:04
  SPEAKER_00: It's worth noting the practical issues.
• 6:06
  SPEAKER_00: Senigermin, oxurvate, drops must be kept frozen and then refrigerated once opened.
• 6:12
  SPEAKER_00: They are packaged in frozen vials with dry ice, and once thawed, should be refrigerated and used within two weeks.
• 6:19
  SPEAKER_00: This makes it a bit cumbersome to use.
• 6:21
  SPEAKER_00: Any NGF or peptide therapy for glaucoma would need similar special handling.
• 6:26
  SPEAKER_00: Measuring success, field tests and imaging.
• 6:29
  SPEAKER_00: In any study of glaucoma treatments, two main outcomes are used visual field tests.
• 6:34
  SPEAKER_00: These map how much of the peripheral vision a patient has.
• 6:37
  SPEAKER_00: A worsening field means more vision is lost.
• 6:40
  SPEAKER_00: Tests report a mean deviation score.
• 6:42
  SPEAKER_00: Optical coherence tomography, OCT, a non-invasive scan that measures the thickness of the retinal nerve fiber layer, the fibers of the ganglion cells.
• 6:52
  SPEAKER_00: Thinning on OCT shows RGC loss.
• 6:55
  SPEAKER_00: The small NGF trial in glaucoma reported better visual field scores after treatment.
• 7:00
  SPEAKER_00: Future studies would also look at OCT scans.
• 7:03
  SPEAKER_00: If NGF truly protects nerve cells, the loss of layer thickness on OCT ought to slow compared to normal glaucoma progression.
• 7:11
  SPEAKER_00: Other measures include visual acuity, contrast sensitivity, and electrophysiology, like pattern ERG or VEP.
• 7:19
  SPEAKER_00: In that uncontrolled case series, all these parameters showed improvement.
• 7:23
  SPEAKER_00: While promising, these findings must be confirmed in controlled trials using the standard measures above.
• 7:29
  SPEAKER_00: Safety and side effects.
• 7:32
  SPEAKER_00: Available data suggest topical NGF is quite safe to use in the eye.
• 7:36
  SPEAKER_00: The main side effects are local irritation.
• 7:38
  SPEAKER_00: In the official prescribing information and studies of Senigermin, about 15 to 16% of patients reported eye pain on using the drops.
• 7:47
  SPEAKER_00: Some people also have redness, inflammation, or tearing.
• 7:51
  SPEAKER_00: These effects are usually mild and resolve after stopping treatment.
• 7:55
  SPEAKER_00: No serious systemic side effects have been reported with ocular NGF.
• 8:00
  SPEAKER_00: The protein doesn't easily enter the bloodstream from the eye.
• 8:03
  SPEAKER_00: In fact, one review noted that systemic absorption is low and most patients have no adverse reactions.
• 8:10
  SPEAKER_00: This contrasts with giving NGF by injections or infusions in the body.
• 8:14
  SPEAKER_00: Decades ago, clinical trials of injectable NGF for neurological diseases found severe pain and muscle aching in patients, which halted those studies.
• 8:24
  SPEAKER_00: The good news is that using NGF in the eye appears to avoid those problems.
• 8:28
  SPEAKER_00: So far, aside from eye irritation, NGF drops have had no major safety issues in small glaucoma studies.
• 8:35
  SPEAKER_00: Peptide memetics would likely share this safety advantage if used topically.
• 8:40
  SPEAKER_00: They are small and non-toxic, but specific data are not yet available.
• 8:45
  SPEAKER_00: In any case, eye treatment avoids the risk of widespread side effects.
• 8:49
  SPEAKER_00: Patients should still watch for eye redness, worsening pain, or allergic signs and report them to their doctor promptly.
• 8:56
  SPEAKER_00: Cost and availability.
• 8:58
  SPEAKER_00: One major hurdle for NGF therapy is cost and access.
• 9:02
  SPEAKER_00: Senegroman Oxurvate is very expensive.
• 9:05
  SPEAKER_00: A recent study found that eight weeks of treatment, the standard course, can run on the order of tens of thousands of dollars per patient.
• 9:11
  SPEAKER_00: For example, Medicare data from 2019 to 2020 show the total spending on Senegarmin was about$287 million for 24-10 patients.
• 9:22
  SPEAKER_00: This works out to an average gross cost of roughly$120,000 per patient per course.
• 9:28
  SPEAKER_00: Out-of-pocket co-pays were typically several thousand dollars, median about$5,800.
• 9:35
  SPEAKER_00: Because of the price, senigermin is usually only covered by insurance when used for the approved cornea disease, not for off-label glaucoma.
• 9:44
  SPEAKER_00: Patients and doctors have to go through special approval or fund the cost privately.
• 9:49
  SPEAKER_00: The drops must be ordered from specialty pharmacies and kept frozen, which adds complexity.
• 9:54
  SPEAKER_00: Peptide therapies, if ever approved, would likely also be costly at first since they are biologic drugs.
• 10:01
  SPEAKER_00: There are no generic versions of senagermin.
• 10:04
  SPEAKER_00: In short, NGF-based treatments are not widely available and remain accessible mainly at major eye centers or through research programs.
• 10:12
  SPEAKER_00: Any discussion of using NGF for glaucoma must consider these cost and access issues.
• 10:17
  SPEAKER_00: Conclusion.
• 10:18
  SPEAKER_00: In summary, growth factor strategies hold promise for saving injured nerve cells in glaucoma, but they are not yet ready for routine use.
• 10:26
  SPEAKER_00: Laboratory and early clinical data hint that NGF can protect retinal ganglion cells and even improve vision in some patients.
• 10:34
  SPEAKER_00: New NGF-like peptides are being designed to mimic this effect.
• 10:38
  SPEAKER_00: However, the only approved NGF eye drop, senedermin, is for a corneal disease.
• 10:44
  SPEAKER_00: Its use in glaucoma would be off-label.
• 10:47
  SPEAKER_00: While that has generated off-label interest, it also means insurers usually do not pay for it.
• 10:52
  SPEAKER_00: Up to now, safety has been acceptable, mostly mild eye pain, but the cost is very high.
• 10:59
  SPEAKER_00: For patients, it is exciting that research is exploring ways to preserve the optic nerve, but no NGF therapy has been proven effective or safe for glaucoma so far.
• 11:09
  SPEAKER_00: Doctors and patients should be cautious.
• 11:11
  SPEAKER_00: If a clinician offers NGF drops for glaucoma, be aware that it's an experimental use.
• 11:17
  SPEAKER_00: The doctor will have to obtain the medications specially and explain that evidence is preliminary.
• 11:22
  SPEAKER_00: More research, larger trials is needed to know whether NGF or its peptides can truly slow vision loss.
• 11:28
  SPEAKER_00: In the meantime, standard glaucoma treatments, eye pressure lowering, remain the best proven strategy, while NGF therapies remain a hopeful but unproven addition.
• 11:38
  SPEAKER_00: Tags.
• 11:39
  SPEAKER_00: Nerve growth factor, neuroprotection, glaucoma, optic nerve, retinal ganglion cells, senogermin, oxurvate, NGF peptides, visual field, OCTLing.
• 11:50
  SPEAKER_00: All links to sources are available in the text version of this article.
• 11:54
  SPEAKER_00: You can find the full article at visualfieldtest.com.
• 11:57
  SPEAKER_00: Thanks for listening.
• 11:58
  SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit visualfieldtest.com.