ATH (ASX) Ana Harrops text modified by ChatGpt

Originally posted by pivalde: ↑

Thanks to Itsagas we have this. It was not very easy to read, however. That is why asked for help and this is the answer:

Apologies for the late response, and thank you for your questions. I reached out to the Alterity team to gather more information. Below is their response:
Key Differences Between ATH434 and Deferiprone
1. Mechanism of Action in Iron Regulation
The article highlights important differences in the mechanisms of action between ATH434 and deferiprone.
ATH434 is designed to address diseases driven by iron-induced oxidative damage.
2. Fe²⁺ as a Catalyst of Oxidative Stress
The form of iron that catalyzes oxidative stress, as depicted in Figure 2, is Fe²⁺.
Our recent publication (Pall et al., 2024) confirms that ATH434 has an affinity for Fe²⁺ similar to endogenous cellular Fe²⁺ chaperones (e.g., glutathione, poly-C-binding proteins).
These proteins regulate Fe²⁺ by:
Supplying Fe²⁺ to enzymes.
Shuttling Fe²⁺ into safe storage.
Facilitating normal iron export.
By enhancing the buffering capacity of these proteins, ATH434 helps limit Fe²⁺'s ability to trigger oxidative stress.
3. Deferiprone's Interaction with Fe²⁺ and Fe³⁺
Under normal cellular conditions, deferiprone is unlikely to bind Fe²⁺ in a meaningful way.
Deferiprone has a much higher affinity for Fe³⁺ than Fe²⁺.
Before deferiprone can "trap" or bind Fe²⁺, an electron is ejected from the Fe²⁺ complex, leading to two key consequences:
a. Conversion of Fe²⁺ to Fe³⁺
Table 1 in the article lists deferiprone as showing positive results in Friedreich’s ataxia (Pandolfo, ref 63).
However, Pandolfo (2013) notes that in a six-month trial, high doses of deferiprone worsened ataxia—similar to symptom worsening in Parkinson’s disease (PD) patients (Devos 2024, ref 55).
In Friedreich’s ataxia, neurons responsible for motor control are already starved of Fe²⁺; converting it to Fe³⁺ accelerates disease progression.
Similarly, in PD, neuromelanin helps aged primate brains sequester Fe²⁺.
However, Fe³⁺ must be converted back to Fe²⁺ for dopamine synthesis, which is critical for motor control.
In Devos (2024), hormonal biomarker data showed that deferiprone depleted central dopamine in a way that correlated with worsened motor function.
Deferiprone’s adverse effect on endogenous dopamine likely reflects unnecessary Fe³⁺ removal from dopamine-synthesizing enzymes, partly due to Fe²⁺ oxidation.
b. Generation of Free Radicals
The ejected electron from Fe²⁺ oxidation contributes to oxidative stress.
This free electron reacts with oxygen, forming hydroxyl radicals (as discussed in Figure 1 of the article).
Free radicals damage intracellular structures, including DNA and lipids, leading to cellular injury.
How ATH434 Differs from Deferiprone
1. ATH434 Is Not an Iron Chelator
ATH434 has a much weaker affinity for Fe³⁺ compared to deferiprone.
However, it has enough affinity to interact with misfolded alpha-synuclein-bound iron in neurons without removing Fe³⁺ from enzymes.
Unlike deferiprone, which forms a complex around Fe³⁺, allowing it to pass freely through membranes and be excreted in urine, ATH434 does not function this way.
Deferiprone removes excess iron from the body (acting as a chelator).
In contrast, ATH434 binds Fe²⁺ or Fe³⁺ without transporting it out of the cell. Instead, iron is transferred to other proteins for normal cellular functions.
2. ATH434 Converts Fe²⁺ to Fe³⁺ at a Much Slower Rate
Pall et al. demonstrated that Fe²⁺ oxidation by ATH434 is significantly slower than with deferiprone.
As a result:
More Fe²⁺ remains safely bound to ATH434 or endogenous chaperones.
Fewer oxygen radicals are generated.
3. ATH434 Has Direct Antioxidant Properties
Unlike deferiprone, ATH434 possesses direct antioxidant properties.
This may help manage oxygen radicals in diseased tissues.
I hope this was helpful. Let us know if you have any further questions.

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Thanks Pivalde, that reads significantly better.

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Last 1.6¢		Change 0.000(0.00%)		Mkt cap ! $147.3M

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1.7¢	1.8¢	1.5¢	$787.6K	48.96M

Ana Harrops text modified by ChatGpt, page-2

Key Differences Between ATH434 and Deferiprone

How ATH434 Differs from Deferiprone

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Ana Harrops text modified by ChatGpt, page-2

Key Differences Between ATH434 and Deferiprone

How ATH434 Differs from Deferiprone

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Listen: HotCopper Wire Podcast 019 – Dreaming of the 9,000s

Boss tanks -42% after quietly flagging 'potential challenges' for Honeymoon

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Clarity confidence – and share price – up on bumper $203M institutional placement

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Buyers (Bids)

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